This study aimed to identify the clinical and biomechanical factors of subjects with excessive foot pronation who are not responsive (i.e., “non-responders”) to medially wedged insoles to increase knee adduction external moment. Ankle dorsiflexion range of motion, forefoot-shank alignment, passive hip stiffness, and midfoot passive resistance of 25 adults with excessive bilateral pronation were measured. Also, lower-limb angles and external moments were computed during walking with the participants using control (flat surface) and intervention insoles (arch support and 6° medial heel wedge). A comparison between “responders” (n = 34) and “non-responders” (n = 11) was conducted using discrete and continuous analyses. Compared with the responders, the non-responders had smaller forefoot varus (p = 0.014), larger midfoot passive internal torque peak (p = 0.005), and stiffness measured by the torsimeter (p = 0.022). During walking, non-responders had lower angle peaks for forefoot eversion (p = 0.001), external forefoot rotation (p = 0.037), rearfoot eversion (p = 0.022), knee adduction (p = 0.045), and external hip rotation (p = 0.022) and higher hip internal rotation angle peak (p = 0.026). Participants with small forefoot varus alignment, large midfoot passive internal torque, stiffness, small knee valgus, hip rotated internally, and foot-toed-in during walking did not modify the external knee adduction moment (“non-responders”). Clinicians are advised to interpret these findings with caution when considering the prescription of insoles. Further investigation is warranted to fully comprehend the response to insole interventions among individuals with specific pathologies, such as patellofemoral pain and knee osteoarthritis (OA).