Objective: To determine how foot structure and lower limb function differ between individuals with and without midfoot osteoarthritis (OA). Design: Electronic databases were searched from inception until May 2020. To be eligible, studies needed to (1) include participants with radiographically confirmed midfoot OA, with or without midfoot symptoms, (2) include a control group of participants without radiographic midfoot OA or without midfoot symptoms, and (3) report outcomes of foot structure, alignment, range of motion or any measures of lower limb function during walking. Screening and data extraction were performed by two independent assessors, with disagreements resolved by a third independent assessor. The methodological quality of included studies was assessed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. Results: A total of 1,550 records were screened by title and abstract and 11 met the inclusion criteria. Quantitative synthesis indicated that individuals who had midfoot OA had a more pronated foot posture, greater first ray mobility, less range of motion in the subtalar joint and first metatarsophalangeal joints, longer central metatarsals and increased peak plantar pressures, pressure time integrals and contact times in the heel and midfoot during walking. Meta-analysis could not be performed as the data were not sufficiently homogenous. Conclusions: There are several differences in foot structure and lower limb function between individuals with and without midfoot OA. Future research with more consistent case definitions and detailed biomechanical models would further our understanding of potential mechanisms underlying the development of midfoot OA.