Background/Objectives: Cutaneous leishmaniasis caused by Leishmania amazonensis is a significant public health issue. This study aimed to evaluate an eco-friendly, thermosensitive nanogel, developed using a low-energy, solvent-free method, incorporating F127 and Carbopol 974P copolymers, and enriched with Pectis brevipedunculata essential oil (EOPb) for its leishmanicidal and anti-inflammatory properties. Methods: The nanogel was prepared and characterized through FTIR, DLS, SEM, and AFM to confirm the incorporation of EOPb, stability and rheological properties. In vitro leishmanicidal activity was evaluated on Leishmania amazonensis promastigotes, and in vivo anti-inflammatory effects were assessed using a rat paw edema model. Results: In vitro, nGF3 (EOPb-loaded nanogel) demonstrated significant leishmanicidal activity, with promastigote mortality rates exceeding 80% at 24 h and 90% at 48 h. In vivo, nGF1, nGF2, and nGF3 exhibited anti-inflammatory effects, with nGF2 and nGF3 reducing edema by 62.7% at 2 h post-treatment. The empty nanogel (nGF0) showed minimal anti-inflammatory activity. Conclusions: The eco-friendly EOPb-loaded nanogel (nGF3) demonstrated strong leishmanicidal and anti-inflammatory effects, presenting a promising candidate for cutaneous leishmaniasis treatment. Further studies are necessary to explore its clinical potential.