Production of biodiesel from microalgae is gaining popularity since it does not compromise food security or the global economy. This article reports biodiesel production with Spirulina microalgae through nanocatalytic transesterification process. The nanocatalyst calcium methoxide Ca(OCH3)2 was synthesized using wet impregnation method and utilized to carry out the transesterification process. The nanocatalyst was characterized to evaluate its structural and spectral characteristics using different characterization techniques such as Thermogravimetric analysis (TGA), X-ray diffraction (XRD), Scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FT-IR), and Brunaeur-Emmett-Teller(BET) measurement for surface area. The result demonstrates that calcium methoxide Ca(OCH3)2 possesses a high catalytic activity compared to a heterogeneous catalyst such as calcium oxide (CaO). The impact of several process parameters such as reaction temperature, the molar ratio of methanol to oil, catalyst concentration, and reaction time used in the transesterification process was optimized by employing central composite design(CCD) based response surface methodology(RSM). The polynomial regression equation of second order was obtained for methyl esters. The model projected a 99% fatty acid methyl esters (FAME) yield for optimal process parameters of reaction time 3hrs,3 wt.% of Ca(OCH3)2 catalyst loading, 80°C reaction temperature, and 30:1 methanol to oil molar ratio.