There is a growing need for novel natural anti-inflammatory agents due to the side effects posed by existing anti-inflammatory compounds. Therefore, the present study aimed to prepare silver nanoparticles (AgNPs) from Crotalaria medicaginea and check their antioxidant potential. After characterizing these AgNPs (using a particle size analyzer, scanning electron microscopy-SEM, and Fourier transform infrared-FTIR analysis), their antioxidant and anti-inflammatory potential was assessed with the help of standard methods, both in vivo and in vitro. Furthermore, mRNA expression for inflammatory markers was determined using qPCR. Results showed that Crotalaria-fabricated silver nanoparticles (C-AgNPs) had strong in vitro antioxidant and anti-inflammatory activities. In vivo studies corroborated the results, demonstrating significant activity as compared with disease and drug control groups. C-AgNPs showed maximum inhibition of inflammation in rats as 69.46, 29.65, and 57.58% in carrageenan-induced paw edema (CPE), cotton pellet-induced granuloma (CPG), and xylene-induced ear edema (XEE), respectively, as compared with other treatments and control. C-AgNPs also upregulated anti-inflammatory markers such as IL-4 (64.22%, 54.41%, and 68.44%) and IL-10 (74.36%, 92.19%, and 92.56%) in all three groups of inflammation studies, respectively. Therefore, the present study concludes that C-AgNPs have potent antioxidant and anti-inflammatory potential. They can also upregulate the antioxidant system and inflammation markers of the living body to boost the immune system.