The main objective of the present study was to explore the potential of matrix tablets as extended release dosage form of tianeptine, using HMPC K100 as a polymer. HPMC K100 extended the release of the drug from formulation due to the gel-like structure. Direct compression method was adopted to compress the tablets using different concentrations of polymer. Tablets were evaluated for pre-compression and post-compression parameters. Drug release study showed that tablet extends the release of drug with the increasing concentration of polymer. Drug, polymers and tablets were analyzed and/or characterized for compatibility, degradation, thermal stability, amorphous or crystalline nature via FTIR, DSC, TGA, XRD studies. SEM study predicted that tablets had a uniform structure. HPMC K100 based tablets were similar to that of the reference product. Acute toxicity study conducted on Swiss albino mice showed that matrix tablets were safe and non-toxic, as no changes in physical activity and functions of organs were observed. Biochemical and histopathological study revealed lack of any kind of abnormality in liver and renal function. Moreover, necrotic changes were absent at organ level.