Cascabela Thevetia, often known as milk bush or yellow oleander, is a diminutive, perennial plant that is mostly used for decorative purposes. The plant seeds are poisonous and thus not attracted to herbivorous animals and are also rich in oil (60–65%). The oleander seed oil being non-edible oil is not used for any purpose. Therefore, for better utilisation, biodiesel could be the best solution. The yield of biodiesel is an essential factor in the entire production process. To maximise biodiesel yield with minimal experimentation, optimisation strategies are often used. In this regard, the Taguchi technique was used to maximise yield by optimising the production factors (i.e., methanol to oil ratio, reaction temperature, reaction time, catalyst concentration) for biodiesel produced from yellow oleander seed oil in the presence of citrus limetta (commonly known as sweet lime)-based heterogeneous catalyst. A total of 9 experiments based on Taguchi L9 orthogonal array were carried out by transesterification process. The results show that the optimum biodiesel yield was 93.134% at a molar ratio of 15:1 with a catalyst concentration of 4.5% by weight and a reaction time of 3 h at 55 °C. Reaction time and catalyst concentration were the most and least influential elements in biodiesel production, with contributing factors of 48.54% and 7.27%, respectively.