During the past decade, various novel tissue engineering (TE) strategies have been developed to maintain, repair, and restore the biomechanical functions of the musculoskeletal system. Silk fibroins are natural polymers with numerous advantageous properties such as good biocompatibility, high mechanical strength, and low degradation rate and are increasingly being recognized as a scaffolding material of choice in musculoskeletal TE applications. This current systematic review examines and summarizes the latest research on silk scaffolds in musculoskeletal TE applications within the past decade. Scientific databases searched include PubMed, Web of Science, Medline, Cochrane library, and Embase. The following keywords and search terms were used: musculoskeletal, tendon, ligament, intervertebral disc, muscle, cartilage, bone, silk, and tissue engineering. Our Review was limited to articles on musculoskeletal TE, which were published in English from 2010 to September 2019. The eligibility of the articles was assessed by two reviewers according to prespecified inclusion and exclusion criteria, after which an independent reviewer performed data extraction and a second independent reviewer validated the data obtained. A total of 1120 articles were reviewed from the databases. According to inclusion and exclusion criteria, 480 articles were considered as relevant for the purpose of this systematic review. Tissue engineering is an effective modality for repairing or replacing injured or damaged tissues and organs with artificial materials. This Review is intended to reveal the research status of silk-based scaffolds in the musculoskeletal system within the recent decade. In addition, a comprehensive translational research route for silk biomaterial from bench to bedside is described in this Review.