Temporomandibular joint (TMJ) discomfort is a prevalent condition affecting a significant portion of the global population, often leading to impaired quality of life and reduced oral functionality. Various treatment modalities have been explored to alleviate TMJ discomfort, with injectable medications emerging as a promising therapeutic approach. This systematic review aims to provide a comprehensive overview of the efficacy of injectable medications in relieving TMJ discomfort. A rigorous search of electronic databases was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The findings are presented in a narrative synthesis, highlighting trends in treatment outcomes and potential complications associated with injectable medications for TMJ discomfort. The Risk‐of‐bias VISualization (Robvis) and the Mixed Methods Appraisal Tool (MMAT) were used as quality assessment tools. This review synthesizes valuable insights from the scientific literature across multiple electronic databases. A total of 25 articles were selected for inclusion in the study. Most patients investigated had been diagnosed with internal derangement of the TMJ. Various injections, including Sodium Hyaluronate (SH), Autologous Blood Injection (ABI), Platelet-Rich Plasma (PRP), and Corticosteroid (CS), were administered to alleviate pain and discomfort. Most studies administered these injections after arthrocentesis or in combination with other injections. The combination of arthrocentesis with additional injections demonstrated superior outcomes compared to the sole use of a single injection. This review underscores the need for further research to optimize the selection and administration of injectable medications for Temporomandibular disorders management. It also emphasizes the importance of a personalized approach, considering individual patient characteristics and preferences in treatment decision-making.