BACKGROUND: Foot orthoses (FOs) are commonly prescribed to reduce pain and improve function in individuals with musculoskeletal disorders, including those with chronic metatarsalgia (CM). Reducing the mechanical overload under the metatarsal heads during locomotion is the central point of the treatment for CM. Medially wedged FOs (MWFOs) with a metatarsal pad could further reduce pressure loading under the metatarsal heads and modify foot and ankle biomechanics compared to standard FOs (SFOs). RESEARCH QUESTION: Do MWFOs further decrease the peak plantar pressure under the metatarsal heads in individuals with CM compared to SFOs? What are the effects of these FOs on foot and ankle 3D kinematics and kinetics in individuals with CM? METHODS: Twenty-three individuals (17 females and 6 males) with CM were recruited in this cross-sectional descriptive study. Participants walked during three conditions: (1) Shod, (2) SFOs, and (3) MWFOs. Peak plantar pressure, midfoot and ankle angles and moments were calculated and compared across conditions with repeated measure ANOVAs using statistical parametric mapping. RESULTS: SFOs and MWFOs reduced plantar pressure under the metatarsal heads, ankle plantarflexion angle, and midfoot plantarflexion moment compared to shod. SFOs and MWFOs increased plantar pressure under the medial midfoot. MWFOs reduced plantar pressure under the 1st-2nd-3rd metatarsal heads during the second part of the stance phase and increased plantar pressure under the medial midfoot compared to SFOs. MWFOs also decreased midfoot dorsiflexion and inversion angles, ankle eversion angle, and ankle inversion moment compared to shod. SIGNIFICANCE: MWFOs were more effective than SFOs in reducing peak pressure under the 1st-2nd-3rd metatarsal heads and modifying lower limb biomechanics during walking. This reduction implies a pressure transfer from the metatarsal heads to the medial midfoot. These findings are promising to find the FOs model most suitable to reduce pain and improve physical function in individuals with CM.