The excessive reliance on fossil fuels has resulted in an energy crisis, environmental pollution, and health problems, calling for alternative fuels such as biodiesel. Here, we review computational chemistry and machine learning for optimizing biodiesel production from waste. This article presents computational and machine learning techniques, biodiesel characteristics, transesterification, waste materials, and policies encouraging biodiesel production from waste. Computational techniques are applied to catalyst design and deactivation, reaction and reactor optimization, stability assessment, waste feedstock analysis, process scale-up, reaction mechanims, and molecular dynamics simulation. Waste feedstock comprise cooking oil, animal fat, vegetable oil, algae, fish waste, municipal solid waste and sewage sludge. Waste cooking oil represents about 10% of global biodiesel production, and restaurants alone produce over 1,000,000 m³ of waste vegetable oil annual. Microalgae produces 250 times more oil per acre than soybeans and 7–31 times more oil than palm oil. Transesterification of food waste lipids can produce biodiesel with a 100% yield. Sewage sludge represents a significant biomass waste that can contribute to renewable energy production.