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Introduction: Neem (Azadirachta indica A. Juss.), a widely used medicinal tree in Ayurveda, is renowned for antimicrobial, anti-inflammatory, and immunomodulatory properties. It is traditionally employed for skin infections, oral health, gastrointestinal disorders, and general detoxification. Modern research has elucidated its phytochemistry and pharmacological activities, but a consolidated review is warranted. Methods: Literature search was performed on PubMed, Scopus, Web of Science, and Google Scholar, along with Ayurvedic texts (Charaka Samhita, Sushruta Samhita, Bhavaprakasha Nighantu). Studies from 1950–2025 covering phytochemistry, pharmacology, and clinical trials were included. Exclusion criteria: anecdotal reports, duplicates, and low-quality studies. Results: Traditional Ayurveda describes Neem as Tikta, Kashaya, Sheeta, with Rakta-stambhana (blood purification), Krimighna (antimicrobial), and Vata-Pitta hara properties. Phytochemicals include limonoids (azadirachtin, nimbin, nimbolide), flavonoids, tannins, and triterpenoids. Pharmacological studies show broad-spectrum antimicrobial, antifungal, antiviral, anti-inflammatory, hepatoprotective, antidiabetic, and anticancer effects. Clinical studies support its use in oral hygiene, dermatological infections, and metabolic disorders. Discussion: Ayurveda’s conceptualization of Neem aligns with modern pharmacology. Its multi-targeted actions validate traditional uses, but standardization, safety, and dose optimization are necessary for clinical application. Conclusion: Neem exemplifies integration of traditional knowledge and modern science. It holds promise as an antimicrobial, immunomodulatory, and systemic therapeutic agent, with potential for development into standardized phytopharmaceuticals.

KEYWORDS: Azadirachta indica, Antimicrobial, Ayurveda, Immunomodulation, Pharmacology