Background: The process of the globally aging population has been accelerating, leading to an increasing social burden. As people age, the musculoskeletal system will gradually go through a series of degenerative and loss of function and eventually develop age-related musculoskeletal diseases, like sarcopenia, osteoporosis, and osteoarthritis. On the other hand, several studies have shown that polyunsaturated fatty acids (PUFAs) possess various important physiological functions on the health of muscles, bones, and joints. Objective: This narrative review paper provides a summary of the literature about the effects and mechanisms of PUFAs on age-related musculoskeletal diseases for the prevention and management of these diseases. Methods: Web of Science, PubMed, Science Direct, and Scopus databases have been searched to select the relevant literature on epidemiological, cellular, and animal experiments and clinical evidence in recent decades with keywords “polyunsaturated fatty acids”, “PUFAs”, “omega-3”, “omega-6”, “musculoskeletal diseases”, “sarcopenia”, “osteoporosis”, “osteoarthritis”, and so on. Results: PUFAs could prevent and treat age-related musculoskeletal diseases (sarcopenia, osteoporosis, and osteoarthritis) by reducing oxidative stress and inflammation and controlling the growth, differentiation, apoptosis, and autophagy of cells. This review paper provides comprehensive evidence of PUFAs on age-related musculoskeletal diseases, which will be helpful for exploitation into functional foods and drugs for their prevention and treatment. Conclusions: PUFAs could play an important role in the prevention and treatment of sarcopenia, osteoporosis, and osteoarthritis.