I took an example from your other question and tried to demonstrate here what is going on. So, for completeness:
We are applying the 6th order finite-difference scheme for numerical differentiation using the following code. First, let's apply it on the constant function of different scale ($C_1, C_2, C_3$):
$$
U(x)=C,\quad x\in[0,1]
$$
Since $\frac{\text{d}U(x)}{\text{d}x}=0$, the expected result of differentiation is a zero-vector.
I used $N$=100 discretization points for
- $C_1=2.5545007\cdot10^2$, shown in blue
- $C_2=2.5545007\cdot10^4$, shown in red (original scale of the problem you described)
- $C_3=2.5545007\cdot10^6$, shown in black
The function (solid lines), as well as it's derivative computed without mean subtraction (circle markers) and with mean subtraction (cross markers) is in the figure below. All crosses are exactly at $0$ (I had to assign a dummy value to display them on the semilog plot), which is an expected behavior for a constant function, as Kirill mentioned in a comment. Because you are passing to the differentiation subroutine (or $U-\text{mean}(U)=0$) vector of zeros.

Now, consider a tiny bit more complicated function
$$
U(x)=C\sin(x),\quad x\in[0,1]
$$
Since $\frac{\text{d}U(x)}{\text{d}x}=C\cos(x)$, you would also expect to get a zero-vector for $\frac{\text{d}U(x)}{\text{d}x}-C\cos(x)$, and the scales of the problem are similar to the ones above with a constant function.

For $\sin$, the mean subtraction did nothing for improving the accuracy of the computed derivative.
So in general, subtracting the mean value (i.e. a constant) does not help too much for functions more complicated than a constant.
Regarding the problem with numerical differentiation being sensitive to round off, you already got several good answers in the comments to both questions.
Matlab code for completeness. The function dss006
is available here.
xmin=0; xmax=1;
N=100;
x=linspace(xmin,xmax,N);
fudge=1E-17;
cU1=2.5545007E+2; cU2=2.5545007E+4; cU3=2.5545007E+6;
U1=cU1*ones(N,1); U2=cU2*ones(N,1); U3=cU3*ones(N,1);
W1=cU1*sin(x); W2=cU2*sin(x); W3=cU3*sin(x);
dUx1=dss006(xmin,xmax,N,U1);
dUx2=dss006(xmin,xmax,N,U2);
dUx3=dss006(xmin,xmax,N,U3);
dUx1p=dss006(xmin,xmax,N,U1-mean(U1))+fudge;
dUx2p=dss006(xmin,xmax,N,U2-mean(U2))+fudge;
dUx3p=dss006(xmin,xmax,N,U3-mean(U3))+fudge;
dWx1=dss006(xmin,xmax,N,W1);
dWx2=dss006(xmin,xmax,N,W2);
dWx3=dss006(xmin,xmax,N,W3);
dWx1p=dss006(xmin,xmax,N,W1-mean(W1))+fudge;
dWx2p=dss006(xmin,xmax,N,W2-mean(W2))+fudge;
dWx3p=dss006(xmin,xmax,N,W3-mean(W3))+fudge;
%% ONLY PLOTTING AFTER THIS POINT
MarkerSize=7; LineWid=2.5; ff=22; MyLineWidth=1.0;
set(groot,'DefaultTextInterpreter','latex');
set(groot,'defaultLegendInterpreter','latex');
set(groot,'defaultAxesTickLabelInterpreter','latex');
figure(1)
ph(1)=semilogy(x,abs(U1),'b-','LineWidth',MyLineWidth);hold on;
p1_str='$|U_1(x)|,\;C_1=2.5545007\cdot 10^2$';
ph(2)=semilogy(x,abs(U2),'r-','LineWidth',MyLineWidth);hold on;
p2_str='$|U_2(x)|,\;C_2=2.5545007\cdot 10^4$';
ph(3)=semilogy(x,abs(U3),'k-','LineWidth',MyLineWidth);hold on;
p3_str='$|U_3(x)|,\;C_3=2.5545007\cdot 10^6$';
ph(4)=semilogy(x,abs(dUx1),'bo','LineWidth',MyLineWidth);hold on;
p4_str='$|\widetilde{dU_1/dx}(x)-0|$';
ph(5)=semilogy(x,abs(dUx2),'ro','LineWidth',MyLineWidth);hold on;
p5_str='$|\widetilde{dU_2/dx}(x)-0|$';
ph(6)=semilogy(x,abs(dUx3),'ko','LineWidth',MyLineWidth);hold on;
p6_str='$|\widetilde{dU_3/dx}(x)-0|$';
ph(7)=semilogy(x,abs(dUx1p),'bx','LineWidth',MyLineWidth);hold on;
p7_str='$|\widetilde{dU_1/dx}(x)-0|$,$-$mean($U_1$)';
ph(8)=semilogy(x,abs(dUx2p),'rx','LineWidth',MyLineWidth);hold on;
p8_str='$|\widetilde{dU_2/dx}(x)-0|$,$-$mean($U_2$)';
ph(9)=semilogy(x,abs(dUx3p),'kx','LineWidth',MyLineWidth);hold on;
p9_str='$|\widetilde{dU_3/dx}(x)-0|$,$-$mean($U_3$)';
title('$U(x)=C$'); grid on; set(gca,'FontSize',ff-2);
xlabel('$x$','FontSize',ff);
ylabel('$|U(x)|, |\widetilde{\frac{dU}{dx}}(x)-\frac{dU}{dx}(x)|$','FontSize',ff);
h=legend([ph(1) ph(2) ph(3) ph(4) ph(5) ph(6) ph(7) ph(8) ph(9)],p1_str,p2_str,p3_str,p4_str,p5_str,p6_str,p7_str,p8_str,p9_str,'Location','Best');
h.FontSize=ff-6; h.EdgeColor=[1. 1. 1.];
ylim([1E-17 1E+9]);
set(gca,'YTick',[1E-15 1E-12 1E-9 1E-6 1E-3 1E-0 1E+3 1E+6 1E+9]);
figure(2)
ph(1)=semilogy(x,abs(W1),'b-','LineWidth',MyLineWidth);hold on;
p1_str='$|U_1(x)=C_1\sin(x)|,\;C_1=2.5545007\cdot 10^2$';
ph(2)=semilogy(x,abs(W2),'r-','LineWidth',MyLineWidth);hold on;
p2_str='$|U_2(x)=C_2\sin(x)|,\;C_2=2.5545007\cdot 10^4$';
ph(3)=semilogy(x,abs(W3),'k-','LineWidth',MyLineWidth);hold on;
p3_str='$|U_3(x)=C_3\sin(x)|,\;C_3=2.5545007\cdot 10^6$';
ph(4)=semilogy(x,abs(dWx1-cU1*cos(x)),'bo','LineWidth',MyLineWidth);hold on;
p4_str='$|\widetilde{dU_1/dx}(x)-C_1\cos(x)|$';
ph(5)=semilogy(x,abs(dWx2-cU2*cos(x)),'ro','LineWidth',MyLineWidth);hold on;
p5_str='$|\widetilde{dU_2/dx}(x)-C_2\cos(x)|$';
ph(6)=semilogy(x,abs(dWx3-cU3*cos(x)),'ko','LineWidth',MyLineWidth);hold on;
p6_str='$|\widetilde{dU_3/dx}(x)-C_3\cos(x)|$';
ph(7)=semilogy(x,abs(dWx1p-cU1*cos(x)),'bx','LineWidth',MyLineWidth);hold on;
p7_str='$|\widetilde{dU_1/dx}(x)-C_1\cos(x)|$,$-$mean($U_1$)';
ph(8)=semilogy(x,abs(dWx2p-cU2*cos(x)),'rx','LineWidth',MyLineWidth);hold on;
p8_str='$|\widetilde{dU_2/dx}(x)-C_2\cos(x)|$,$-$mean($U_2$)';
ph(9)=semilogy(x,abs(dWx3p-cU3*cos(x)),'kx','LineWidth',MyLineWidth);hold on;
p9_str='$|\widetilde{dU_3/dx}(x)-C_3\cos(x)|$,$-$mean($U_3$)';
title('$U(x)=C\sin(x)$'); grid on; set(gca,'FontSize',ff-2);
xlabel('$x$','FontSize',ff);
ylabel('$|U(x)|, |\widetilde{\frac{dU}{dx}}(x)-\frac{dU}{dx}(x)|$','FontSize',ff);
h=legend([ph(1) ph(2) ph(3) ph(4) ph(5) ph(6) ph(7) ph(8) ph(9)],p1_str,p2_str,p3_str,p4_str,p5_str,p6_str,p7_str,p8_str,p9_str,'Location','Best');
h.FontSize=ff-6; h.EdgeColor=[1. 1. 1.];
ylim([1E-17 1E+9]);
set(gca,'YTick',[1E-15 1E-12 1E-9 1E-6 1E-3 1E-0 1E+3 1E+6 1E+9]);