Spherical crystallization is a promising process intensification technique, where surfactant is an important ingredient in formulation but needs to be used carefully due to toxicological reasons. This work proposes to substitute the conventionally used surfactants by adopting colloidal particles stabilized Pickering emulsions for spherical crystallization. A representative system is selected for study, where silica nanoparticles are prepared to stabilize emulsions and evaporative crystallization of ibuprofen is carried out. Depletion attraction is exploited to improve the Pickering emulsion stability for better confining on crystallization with two depletants PEG and PVA tested. Crystal products from the emulsions prepared with silica nanoparticles and the non-ionic surfactant Tween 20 are compared. The results show that depletion attraction is helpful for producing stable Pickering emulsions with high dispersed phase fraction and mono-dispersed ibuprofen spherical agglomerates. Silica nanoparticles contribute to reduced induction time by boosting heterogeneous nucleation and mitigate secondary agglomeration possibly by steric effects.