A simple, precise, accurate and reproducible spectrophotometric method has been developed for simultaneous estimation of Lornoxicam (LXM) and Eperisone (EPE) by employing first order derivative zero crossing method in methanol. The first order derivative absorption at 264.5 nm (zero cross point of LXM) was used for quantification of EPE and 254 nm (zero cross point of EPE) for quantification of LXM. The linearity was established over the concentration range of 2–24 μg/ml with correlation coefficient 0.9987 and 0.997, respectively. The mean % recoveries were found to be in the range of 99.69 and 99.13 for LXM and EPE respectively. The developed method has been validated as per ICH guidelines and successfully applied to the estimation of LXM and EPE in their Synthetic Mixture.