Spherical silica particles are typically made via Stöber processes. However, these processes are environmentally unsustainable. Here, we report a process to synthesise spherical silica particles in a more sustainable way using sodium caseinate. Initial experiments showed that sodium caseinate can replace the typical industrial structural directing agents used to produce spherical particles. Particles of 124 nm in size were produced with 200 mg L−1 sodium caseinate and 81 µL sodium silicate, and particles with a bimodal size distribution (258 and 1432 nm) were produced with 400 mg L−1 sodium caseinate and 81 µL sodium silicate. Particles with multimodal size distributions between 363–1588 nm and 342–860 nm where produced with 200 mg L−1 sodium caseinate and 162 µL sodium silicate and 200 mg L−1 sodium caseinate and 810 µL sodium silicate, respectively. Higher concentrations of sodium caseinate and low concentrations of sodium silicate promoted Ostwald ripening. Low concentrations of sodium caseinate and high concentrations of sodium silicate promoted coalescence. Subsequent optimisation of the monodispersity using a statistical design of experiments yielded size-monodisperse silica particles with a narrower size distribution between 172 and 340 nm using sodium caseinate, calcium chloride, sodium silicate, and acetate buffer. Analysis of variance (ANOVA) and regression analyses were used to determine and quantify the relationship between reagent concentrations and particle size. A regression equation was calculated, which predicts particle size based on reagent concentration. Predicted particle sizes (189.6, 197.1, 204.6, and 212.1 nm) and experimentally determined particle sizes (200, 190, 184, and 196 nm) showed good agreement. The possibility of producing spherical silica particles sustainably is shown.