The objective of the present study is to formulate and evaluate the mouth-dissolving sublingual tablet of Desvenlafaxine by direct compression method.The sublingual tabletwas manufactured using a direct compression method and using various super disintegrant concentrations. Superdisintegrant such as Sodium starch glycolate (SSG) and Croscarmellose sodium (CCS) is used. IR Spectroscopy and Differential scanning calorimetry were used to conduct compatibility tests on drugs and polymers. The tablet was evaluated for pre-compression studies such as Tapped density, Bulk density, Angle of repose, Carr’s index, and Hausner’s ratio &post-compressions studies like Hardness, Thickness,Weight variation, Friability, Wetting time, Drug content, Disintegration time and In vitro drug release study.There was an interaction between drug-polymerin accordance with FTIR spectra and DSC studies.Precompression variables passed pharmacopoeial specifications and were all within acceptable ranges. An optimized formulation is an F3 batch among all theformulations. The obtained results showed that the disintegration time of the optimized batch (was 30 sec.to 68 sec). The best in vitro drug release was found to be in the F3 batch is102%.Sublingual tablets of Desvenlafaxine were successfully prepared by using two different super disintegrants with good bioavailability.