This study introduces an innovative way to use calcium oxide (CaO) derived from mussel shells as a catalyst support for biodiesel production. Several transition metals, including Ni, Ag, Mo, Co, and W were loaded on the aforementioned support to synthesize mono-metallic and bi-metallic catalysts using the wet impregnation method. Microwave technology was utilized to accelerate reactions and improve efficiency. Characterization techniques such as BET, SEM/EDX, and XRD confirmed the successful incorporation of metals into the catalyst structure. The prepared catalysts, Mussel(Ni), Mussel(Ni-W), Mussel(Ni-Ag), Mussel(Ni-Mo), and Mussel(Ni-Co), were evaluated to investigate the catalytic performance for biodiesel production from corn oil under different conditions such as microwave powers, catalyst loadings, reaction times, and methanol-to-oil ratios. The combination of mussel-derived catalysts with microwave technology resulted in reduced reaction times and 100% selectivity under conditions of 1.5% catalyst loading, 10 min reaction time, and a methanol-to-oil ratio of 15:1, showcasing the synergistic effects of transition metals. This study highlights the potential of mussel-shell-derived catalysts as a cost-effective and sustainable solution for biodiesel production. By reducing reliance on conventional methods, these findings contribute to clean energy advancements and offer a scalable, environmentally friendly pathway for renewable fuel synthesis.