Provided are a drive compensation method and system of a display panel and a display device. The drive compensation method includes: determining at least one of the impedance and capacitive reactance variation curve of a first signal line in a column direction and determining the charge rate variation curve of first pixel units in a row direction; determining the compensation coefficients for a respective pixel unit in the column direction and/or the row direction according to the impedance and capacitive reactance variation curve of the first signal line in the column direction and/or the charge rate variation curve of first pixel units in the row direction; and compensating the compensation coefficients for the respective pixel unit in the column direction and/or the row direction to the drive signal of the respective pixel unit to drive the respective pixel unit.