The study of phytotherapy in dentistry holds great relevance because of the scarcity of research conducted on the treatment of oral pathologies, specifically, caries and periodontal disease. Therefore, this research aimed to analyze the chemical composition of extracts fromCouroupita guianensisAubl. leaves, evaluate their toxicity, and assess their antioxidant and antimicrobial properties againstStaphylococcus aureus,Streptococcus mutans, andCandida albicans. Three extracts were prepared using assisted ultrasound and the Soxhlet apparatus, namely, Crude Ultrasound Extract (CUE), Crude Soxhlet Extract (CSE), and the Ethanol Soxhlet Extract (ESE). Flavonoids, tannins, and saponins were detected in the chemical analysis, while LC-DAD analysis revealed the presence of caffeic acid, sinapic acid, rutin, quercetin, luteolin, kaempferol, and apigenin in all extracts. GC-MS analysis identified stigmasterol and β-sitosterol in the CUE and CSE. The ESE showed higher antioxidant activity (2.98 ± 0.96 and 4.93 ± 0.90) determined by the DPPH• and ABTS•+methods, respectively. In the toxicity evaluation, the CUE at 50 μg/mL and the ESE at 50 μg/mL stimulated the growth ofAllium ceparoots, while all extracts inhibited root growth at 750 μg/mL. None of the extracts exhibited toxicity againstArtemia salina. Antibacterial activity was observed in all extracts, particularly against the microorganismsS. aureusandS. mutans. However, no antifungal activity againstC. albicanswas detected. These results suggest that extracts ofC. guianensishave therapeutic potential for controlling microorganisms in the oral microbiota.