Background/Objectives: Patellofemoral syndrome is a common osteoarticular condition that affects many individuals. Various treatment options are available, with a significant emphasis on targeted muscle-strengthening exercises. The purpose of this study was to investigate the effect of isokinetic muscle strengthening on muscle strength, joint range of motion, quality of life, physical performance, and pain tolerance in overweight/obese women with patellofemoral syndrome. Methods: Twenty-four overweight or obese women with patellofemoral syndrome participated in the study during September and October 2023 in a private medical facility for physical medicine and functional rehabilitation. They were randomly assigned to one of two groups for six weeks of isokinetic muscle strengthening. The first group (ISO.G) followed a rehabilitation program combined with isokinetic muscle strengthening. A second group (PCM.G) followed a rehabilitation program that includes an isokinetic protocol in passive compensation movement. The extensors’ peak torque was measured before and after training. Results: The flexors’ peak torque, stair climbing test, 10 m walk, chair lift, monopodal support, goniometric knee flexion test, heel–buttock distance measurement, pain, and quality of life scores improved significantly in both groups. The ISO.G, on the other hand, benefited from a significant increase in quadriceps muscle strength revealed by the extensors’ peak torque. Conclusions: For the treatment of patellofemoral syndrome, isokinetic muscle strengthening in concentric mode appears to have a significant advantage over the classic rehabilitation program with isokinetic passive compensation, particularly in muscle strength gain, in addition to the improvement of joint range of motion, quality of life, physical performance, and pain tolerance. Isokinetic training may be recommended as a beneficial approach for the rehabilitative treatment of patellofemoral pain syndrome in overweight/obese women.