This systematic review aimed to 1) verify bilateral symmetry assumption in manual wheelchair (MWC) propulsion in daily-life and sports, and its relationship with injury risk and sports performance; 2) evaluate methods for assessing bilateral symmetry. Scopus, Web-Of-Science, PubMed, and EBSCO databases were searched for articles published before January 2024 investigating bilateral symmetry in MWC users and/or healthy participants during MWC propulsion. Two independent reviewers screened, extracted data, and assessed methodological quality of retrieved papers. Twenty-five studies were included. In daily ground-level propulsion, minimal asymmetries were observed in kinematic, kinetic, and temporal parameters when averaging ≥3 push cycles. In the sports context, diverse findings emerged, ranging from up to 27% side-to-side differences in propulsion kinetics and kinematics during sprinting, to descriptions of both symmetrical and asymmetrical upper extremity motions. Limited evidence exists regarding the role of asymmetry in MWC propulsion as a risk factor for injury and pain, as well as the association between sprinting performance and symmetry. In conclusion, bilateral symmetry assumption in MWC propulsion is valid only under specific conditions (i.e., slow/moderate speed, averaging ≥3 push cycles, smooth level ground). The wheeling environment and inter-individual variability impact symmetry research outcome and require consideration in future studies.