Background. Although foot orthosis may play a role in treatment of patellofemoral pain syndrome, its significance is still conflicting and previous studies show a low level of evidence. Objective. To find the latest evidence regarding the effectiveness of foot orthosis (FO) on adult patients with patellofemoral pain syndrome (PFPS). Methods. A comprehensive electronic database search of PubMed, Cochrane Library Database, the Physiotherapy Evidence Database (Pedro), ProQuest, EBSCo host, and Ovid databases was performed for randomized controlled trials (RCTs) in English language since January 2000 till February 2019 on adults with patellofemoral pain syndrome treated by foot orthosis and physical therapy, with hand searching to reference lists of previous systematic reviews and included papers. At least one primary outcome measure for pain or function must have been reported. Two authors independently reviewed and assessed each citation for inclusion, The Cochrane risk of bias tool was used to rate methodological quality and risk of bias. Data was met analyzed when this was not possible, qualitative data analysis was performed. Results. A total of 9 RCTs with a total number of 415 patients (6 on non-runners and 3 on runners) were included. Findings were summarized in four main comparisons as follows 1)foot orthosis versus flat insoles these results showed the positive efficacy of FO on pain, function and muscular activity, 2) foot orthoses alone versus physiotherapy have a poor indication of PFO alone as an intervention alternative to physiotherapy for PFPS, 3)foot orthoses versus no treatment may provide greater improvements on pain, function and neuromotor changes than natural history concerning foot posture, and 4)foot orthoses combined physiotherapy is better than physiotherapy alone even though the success may relate to clinical foot predictors for foot orthosis. Conclusion. The clinical efficacy of foot orthoses may correlate with targeting specific individuals based on specific foot measures and the comfort perception of the orthosis. On the kinematics, foot orthosis may behave minor neuromotor activity changes at the lower extremity. The effects of combining foot orthoses with physical therapy may be superior to physical therapy alone and result in better outcomes.