Biodiesel as a renewable and environmentally friendly fuel can be considered an alternative to fossil fuel in industries, and one of the promising approaches to developing biodiesel yield is its production in microreactors. However, the produced quantity from microreactors is limited which necessitates higher throughput microreactors to be produced, maintaining the high yield of biodiesel. Therefore, this study investigated the transesterification of waste cooking oil (WCO) with methanol in the presence of sodium hydroxide as the catalyst using a novel branched microreactor, used for higher throughput applications. Thus, a novel four-micro serpentine-based microreactor was designed and fabricated with no external tubing. Biodiesel is produced in the fabricated microreactor and the Box-Behnken Design method (BBD) in Minitab software was used to design the experiments with different operating conditions: methanol to oil molar ratio (6:1–12:1), catalyst concentration (0.5–1.5 wt%), and reaction temperature (55–65 °C) to optimize the biodiesel volume yield in the designed microreactor. The optimum biodiesel yield using GC–MS analysis was found to be 82.8 % at a methanol to oil molar ratio of 12:1, 1.5 wt% catalyst concentration, and reaction temperature of 59.4 °C while maintaining the reactants’ inlet flow rate of 20 µL/s. Production of up to 35 mL biodiesel was collected in 30 min only. In addition, the microreactor achieved up to 97 % conversion at inlet flow rates of 8.5 µL/s.