Inflammatory pain involves the release of cytokines that sensitize nociceptors peripherally. Many synthetic drugs have been used to treat this condition; however, they are mired with a high incidence of side effects and risk of co-morbidities. For this reason, we explored new bioactive compounds characterised by different polarity and chemical structure that could potentially enhance their pharmacological action and bioavailability. Two molecules were obtained through chemical synthesis: scopoletin-cysteine and scopoletin-tryptophane, belonging to the coumarin family. We evaluated the analgesic and anti-inflammatory activity of pure scopoletin and its two derivatives (1 µg/mL), administered topically once daily for 10 days in a model of inflammatory pain induced by CFA (Complete Freund’s Adjuvant) in 5-month-old Wistar rats both male and female. We assessed the responses to mechanical and thermal stimuli, and the extent of paw oedema. Specific histochemical staining was performed to evaluate neutrophil infiltration, mast cells, and collagen deposition. Levels of pro-inflammatory cytokines and the antioxidant system were determined via qRT-PCR. We examined the expression of nociceptive markers in skin terminals. Scopoletin-cys and scopoletin-trp exhibited anti-allodynic analgesic activity from day 3 of treatment. Scopoletin showed only anti-edematous activity. Scopoletin-cys led to changes in IL-6 and TNF-a levels and a reduction in mast cell infiltration.