An organic base catalyst and combinations with animal shells and a metal oxide were tested for biodiesel production. The purpose was the application of these catalyst formulations for biodiesel production in small-scale plants at mild operating conditions. The optimum reaction conditions for the transesterification of vegetable oil were determined. The organic base at optimum conditions produces a biodiesel yield of 93%. Experimental results demonstrate that the synergistic effect of natural catalysts and metal oxide allows the substitution of the expensive catalyst by up to 30% while increasing the biodiesel yield.