In this work, calibration and correction of cross-talk in atomic force microscopy (AFM) is demonstrated. Several reasons and effects of this inherent problem on experimental results are discussed. We propose a general procedure that can be used on most AFM systems to compensate for cross-talk on the cantilever bending and twisting signals. The method utilizes two initial experiments on a flat surface to achieve an affine transformation between the measured signals and the actual signals. Using this transformation directly on the voltage signals allows us to remove the detrimental effects of cross-talk on AFM-based force measurement experiments. The achieved transformation matrix can be turned into a simple circuit and applied online, by users who have access to the raw signals in the AFM head. As a case study, a lateral deflection based mechanical characterization test for a poly(methyl methacrylate) microfiber that is suspended on a trench is investigated in terms of the effectiveness of the cross-talk compensation.