The combination of dapagliflozin propanediol monohydrate and bisoprolol fumarate is indicated for patients with type 2 diabetes mellitus with blood pressure or cardiovascular risks and has been approved by the Central Drugs Standard Control Organization (CDSCO). This work presents a simple, selective, precise, and accurate stability-indicating instrumental thin-layer chromatography (TLC) method for the simultaneous quantification of dapagliflozin propanediol monohydrate and bisoprolol fumarate in bulk and tablet. A polar stationary phase consisting of precoated silica gel G60 F254 aluminum sheet (10 × 10 cm, 0.2 mm layer thickness) and a mobile phase consisting of a mixture of methanol‒ethyl acetate‒25% ammonia (0.5:6:0.3, V/V) were selected. Well-resolved peaks of both drugs were obtained at RF values of 0.24 and 0.46 for dapagliflozin propanediol monohydrate and bisoprolol fumarate, respectively, at an analytical wavelength of 223 nm. The method was observed to be linear in the range of 800‒3200 ng/band for dapagliflozin propanediol monohydrate and 400‒1600 ng/band for bisoprolol fumarate with a correlation coefficient (R2) of 0.9998 for dapagliflozin propanediol monohydrate and 0.9986 for bisoprolol fumarate. Fractional factorial design was employed to assess the robustness of the optimized method. Forced degradation was performed to study the intrinsic stability of both drugs in acidic, basic, oxidation, thermal, and light conditions. Bisoprolol fumarate showed significant degradation in acidic and oxidative conditions, while dapagliflozin propanediol monohydrate showed stability in all conditions applied. The proposed method was validated as per the International Council for Harmonisation (ICH) Q2 (R2) guideline and was found to be robust, accurate, precise, reproducible, and specific for the simultaneous quantification of both drugs in bulk and tablet.