To plot a signal from a .mat file in MATLAB, the user needs to load the data using the 'load' command. The code attempts to extract the size of the loaded data, but it incorrectly uses 'size' on the filename instead of the actual data variable. A proper approach involves creating an x vector that matches the length of the y-data for plotting. The user also seeks assistance with loading the .mat file correctly and using a GUI to select the .m file for execution. Clarifying the data variable after loading the .mat file is essential for successful plotting.