The Brazilian Caatinga green propolis (GP) is known for its significant biological activities
however, its incorporation into pharmaceutical formulations is hindered by its resinous nature and low solubility. This study investigates the analgesic and anti-inflammatory effects of both free GP and nanoencapsulated GP (GPN). The optimized oil/water nanoformulation maintained stability over a period of 28 days, exhibiting minimal alterations in particle size (approximately 200 nm) and polydispersity index (PdI). GPN demonstrated notable inhibition of nociception at a concentration of 27 mg/kg in mice during the formalin test. In the thermal stimulus test, GP exhibited significant analgesic effects at 9 and 60 mg/kg in phase I, whereas GPN achieved this effect at 9 mg/kg. In phase II, GP at 90 mg/kg showed analgesic effects in response to thermal stimuli. GPN also reduced edema from the third hour onward at 9 mg/kg, matching the effects of higher GP concentrations (90 mg/kg). These findings underscore the enhanced efficacy of GPN. Although this preliminary formulation requires further optimization, it demonstrated promising biological activity in the evaluated assays.