Hybrid systems of nanoparticles and polymers have emerged as a new material in the biomedical field. To date, various kinds of hybrid systems have been introduced and applied to drug delivery, regenerative medicine, therapeutics, disease diagnosis, and medical implantation. Among them, the hybridization of nanostructured porous silicon nanoparticles (pSiNPs) and biocompatible polymers has been highlighted due to its unique biological and physicochemical properties. This review focuses on the recent advances in the hybrid systems of pSiNPs and biocompatible polymers from an engineering aspect and its biomedical applications. Representative hybrid formulations, (i) Polymer-coated pSiNPs, (ii) pSiNPs-embedded polymeric nanofibers, are outlined along with their preparation methods, biomedical applications, and future perspectives. We believe this review provides insight into a new hybrid system of pSiNPs and biocompatible polymers as a promising nano-platform for further biomedical applications.