Immense use of fossil fuels leads to various environmental issues, including greenhouse gas emissions, reduced oil reserves, increased energy costs, global climate changes, etc. These challenges can be tackled by using alternative renewable fuels such as biodiesel. Many studies reported that biodiesel production from microalgae biomass is an environment-friendly and energy-efficient approach, with significantly improved fuel quality in terms of density, calorific value and viscosity. Biodiesel is produced using the transesterification process and the most sustainable method is utilizing enzymes for transesterification. Lipase is an enzyme with excellent catalytic activity, specificity, enantio-selectivity, compatibility and stability and hence it is applied in microalgae biodiesel production. But, difficulty in enzymatic recovery, high enzyme cost and minimal reaction rate are some of its drawbacks that have to be addressed. In this aspect, the nanotechnological approach of lipase immobilization in producing microalgae biodiesel is a promising way to increase production yield and it is due to the adsorption efficiency, economic benefit, recyclability, crystallinity, durability, stability, environmental friendliness and catalytic performance of the bio-nanoparticles used. Through increasing post-harvest biomass yield, absorption of CO2 and photosynthesis in the photobioreactor, the use of nanoparticle immobilized lipase during the generation of biodiesel from microalgae has the potential to also remove feedstock availability constraints. This review article discusses the production of microalgae biodiesel, and effect of nanoparticles and immobilized lipase nanoparticles on biodiesel production. The advantages of using lipase nanoparticles and the challenges in introducing the immobilized lipase on nanoparticles in large-scale microalgae biodiesel production are also discussed. Reducing the water and land use, energy and nutrient footprints of integrated algae-based operations must be the main goal of larger-scale experiments as well as ongoing research and development in order to expedite the adoption of microalgae-based biodiesel production. Also, the cost-effectiveness and large-scale availability of nanoparticles and the impact of lipase nanoparticles on engine performance should be analyzed for commercialization of microalgae biodiesel.