Solanum pubescens Willd is an essential ethnomedicinal plant in treatment of hemorrhoids, inflammation, cancer, whooping cough, rheumatoid arthritis, liver disorders, diarrhea, headache, menstrual pain, tuberculosis, ulcers, and belongs to Southern states of India. Henceforth, to validate its medicinal uses concerning the inflammation management the current study aims to evaluate the acute toxicity, in vitro antioxidant efficacy and in vivo anti-inflammatory action of hexane and chloroform extracts of S. pubescens fruits and stem in carrageenan and cotton pellet-induced inflammation in rats. The investigations revealed that the S. pubescens fruit essential oil (SPFO), S. pubescens fruit chloroform extract (SPFC), S. pubescens stem hexane extract (SPSH) and S. pubescens stem chloroform extract (SPSC) demonstrated substantial 2,2diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radicles (OH •), superoxide anion radicles (SOR), nitric oxide radicles (NOR), 2,4,6-tripyridyl-s-triazine (TPTZ) radicle scavenging effect, lipid peroxidation inhibition, total reducing power and total antioxidant activity. The extracts treatment (200 mg/ kg) exhibited significant in vivo anti-inflammatory impact by inhibiting carrageenan-induced paw edema and the weight of cotton pellet-induced granuloma in rats. The current observations might be valuable in strengthening the ethnomedicinal use and considering S. pubescens as a pool of novel anti-inflammatory agents.