Rheumatic and immunological diseases affect multiple systems throughout the body, presenting significant challenges in treatment and management. In recent years, biological agents have been widely applied in the field of rheumatology and immunology, primarily restoring immune balance by targeting and regulating key cells or factors within the immune system. However, this targeted action also introduces safety concerns that warrant focused attention. This article aims to discuss the safety and adverse reactions of biological agents commonly used in clinical rheumatology practice, including tumor necrosis factor-α antagonists, interleukin (IL)-6 antagonists, T-cell co-stimulation inhibitors, IL-17 antagonists, and B-cell-targeted therapeutic drugs, in order to provide a reference for rational clinical drug use.