Osteochondral repair remains a challenge in clinical practice nowadays despite extensive advances in tissue engineering. The insufficient recruitment of endogenous cells in the early stage and incomplete cell differentiation in the later stage constitute the major difficulty of osteochondral repair. Here, a novel all-silk-derived multifunctional biomaterial platform for osteochondral engineering is reported. The bilayer methacrylated silk fibroin (SilMA) hydrogel was fabricated through stratified photocuring as the basic provisional matrix for tissue regeneration. Platelet-rich plasma (PRP) incorporation promoted the migration and pre-differentiation of the bone marrow mesenchymal stem cells (BMSCs) in the early stage of implantation. The long-term regulation of BMSCs chondrogenesis and osteogenesis was realized by the stratified anchoring of the silk fibroin (SF) microspheres respectively loaded with Kartogenin (KGN) and berberine (BBR) in the hydrogel. The composite hydrogels were further demonstrated to promote BMSCs chondrogenic and osteogenic differentiation under an inflammatory microenvironment and to achieve satisfying cartilage and subchondral bone regeneration with great biocompatibility after 8 weeks of implantation. Since all the components used are readily available and biocompatible and can be efficiently integrated via a simple process, this composite hydrogel scaffold has tremendous potential for clinical use in osteochondral regeneration.© 2022 The Authors. Published by Elsevier Ltd.