Background: Family caregivers play a crucial role in the overall healthcare system and in our society. The elderly population is significantly increasing, which creates a high demand for family caregivers. Few studies have investigated the impact of caregiving on musculoskeletal pain or proposed an active approach for dealing with it. Objectives: To determine and characterize musculoskeletal pain in female family caregivers (FFCs) and assess the effects of adding a therapeutic exercise program to a family caregiver care program (FCCP) on the quality of life, physical conditions, and psychological well-being of FFCs. Methods: A multicenter randomized controlled clinical trial was conducted with 68 FFCs recruited in two public healthcare areas. The intervention and control groups received the same conventional FCCP for 6 h across 4 sessions. The intervention group received an additional 36 sessions of physical therapeutic exercise (PTE) program over 12 weeks. Results: All caregivers reported having pain in particular locations. Lower back pain and neck pain were the locations most frequently cited, with a prevalence of 69.4% and 56.7%, respectively. In total, 80% of participants presented moderate pain intensity. The intervention group showed a significant decrease in the intensity of the pain (p < 0.001), as well as in anxiety, depression, subjective burden perception (p < 0.01), and quality-of-life variables, including MCS (mental component summary) (p < 0.05) and PCS (physical component summary) (p < 0.001). Conclusions: A PTE program improved the musculoskeletal pain of FFCs in a clinically relevant way. The caregivers who improved the most were those who initially presented the most intense pain, had the greatest levels of disability, and had the lowest quality of life.