Abstract Chronic inflammation underlies diseases such as autoimmune disorders, cardiovascular conditions, and cancer. Conventional anti‐inflammatory therapies often cause adverse effects and drug resistance, necessitating safer alternatives. This study reports the green synthesis of silver nanoparticles (AgNPs) using Ipomoea cairica leaf extract (ICLE) and evaluates their anti‐inflammatory potential. Synthesis of AgNPs was optimized for extract and silver nitrate concentrations, temperature, time, pH, and reactant ratios, with ultraviolet‐visible (UV‐Vis) spectroscopy monitoring maximal surface plasmon resonance (SPR) and minimal particle size. Characterization included UV‐Vis and Fourier transform infrared (FT‐IR) spectroscopic analyses, particle size and zeta potential analyses, energy‐dispersive X‐ray analysis (EDAX), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and X‐ray diffraction (XRD), confirming spherical AgNPs (30–110 nm) with a face‐centered cubic structure. In vitro assays demonstrated inhibition of protein denaturation and cyclooxygenase‐2 (COX‐2) activity (IC 50 = 60.02 µg/mL), comparable to acetylsalicylic acid and celecoxib, while antioxidant activity approached that of ascorbic acid. Furthermore, in vivo evaluation using the carrageenan‐induced paw edema model showed that AgNPs at 150 mg/kg effectively suppressed inflammation, with inhibition rates comparable to the standard NSAID indomethacin. Thus, the study emphasizes the translational potential of the synthesized AgNPs as eco‐friendly and biocompatible alternatives for inflammation management.