The plants Agave sisalana (sisal) and Punica granatum (pomegranate) are rich in saponins, which are secondary metabolites known for their therapeutic properties, including anti-inflammatory effects. Although, Brazil is the world's leading sisal producer, approximately 95% of the leaves are discarded after fiber extraction. Similarly, pomegranate peel waste is abundant in Brazil. To address the need for safe and effective anti-inflammatory treatments. This study aimed to create a topical mucoadhesive gel containing a combination of sisal (RS) and pomegranate residue ex-tracts (PR). In vitro experiments examined isolated and combined extracts, as well as the result-ing formulation, focusing on: 1) phytochemical analysis (total saponin content); 2) cytotoxicity (MTT assay); and 3) pharmacological assessment of anti-inflammatory activity (phagocytosis, macrophage spreading, and membrane stability).Results revealed saponin concentrations in grams per 100 grams of dry extract as follows: SR - 29.91 ± 0.33, PR - 15.83 ± 0.93, Association (A) - 22.99 ± 0.01, Gel Base (G1) - 0.00 ± 0.00, and Association Gel (G2) - 0.52 ± 0.05. In MTT tests for isolated extracts, cytotoxicity values (µg/mL) were 3757.00 for SR and 2064.91 for PR. Converse-ly, A and G2 exhibited no cytotoxicity, with increased cell viability over time. All three anti-inflammatory tests confirmed the presence of this activity in SR, PR, and A. Notably, G2 demon-strated an anti-inflammatory effect comparable to dexamethasone.In conclusion, the gel contain-ing SR and PR holds promise as a novel herbal anti-inflammatory treatment. Its development could yield economic, social, and environmental benefits by utilizing discarded materials in Brazil.