Strontium titanate was synthesized by polymer precursor method and its catalytic activity as heterogeneous basic catalyst was tested in transesterification reaction for high-quality biodiesel production form Madhuca indica oil. The synthesized strontium titanate was characterized by powder X-ray Diffraction (XRD), X-Ray Photoelectron Spectroscopy (XPS), Field Emission Scanning Electron Microscopy (FESEM) attached with Energy Dispersive X-ray Spectroscopy (EDS), Transmission Electron Microscopy (TEM), Fourier Transform Infrared Spectroscopy (FTIR). Surface area and basicity were also determined using Brunauer-Emmett-Teller (BET)surface area analyzer and Hammett indicator method. The structural characterizations of catalyst enunciated the single perovskite phase formation of well-assorted strontium titanate nanospheres. The transesterification reaction was optimized using one variable at a time (OVAT) and Response Surface Methodology (RSM) using Box Behnkehn Design (BBD) to comprehend the linear effect and interactive effect of process variables on biodiesel production. The optimized reaction condition through OVAT was obtained as: catalyst dose (1.3 wt%), methanol to oil molar ratio (18:1), reaction temperature (65 °C), reaction time (120 min), and agitation speed (600 rpm) while RSM predicted the highest methyl ester conversion at optimum catalyst dose (1.19 wt%), methanol to oil molar ratio (21.5:1), reaction temperature (71 °C), and reaction time (97.7 min). The confirmatory experiment noticed the highest 98% FAME conversion at following reaction conditions catalyst dose (1.2 wt%), methanol to oil molar ratio (22:1), reaction temperature (65 °C), and reaction time (100 min). Confirmatory experiment showed its close agreement with the predicted values from RSM instead OVAT. According to RSM, catalyst dose, reaction temperature, reaction time, and methanol to oil molar ratio were influencing process parameters for transesterification in descending order of their strength. Furthermore, a pseudo-first-order kinetic model was established with the activation energy (Ea) of 65.95 kJ mol−1. The Environmental Factor (E-factor) and Turn Over Frequency (TOF) were also determined and demonstrated the prepared catalyst as a sustainable and potential heterogeneous base catalyst. The physicochemical properties of produced biodiesel were evaluated to check its compatibility with conventional diesel fuel.