Spermacoce latifolia and Celastrus paniculatus are two medicinal plants with significant ethnobotanical relevance and diverse pharmacological activities. Spermacoce latifolia, commonly used in traditional medicine for its anti-inflammatory, antimicrobial, antioxidant, neuroprotective, and anti-diabetic properties, contains bioactive compounds such as flavonoids, alkaloids, and phenolic compounds. These compounds exert their effects through the inhibition of pro-inflammatory pathways, scavenging of free radicals, and modulation of metabolic and neurological functions. Celastrus paniculatus, known as the intellect tree, is prominent in Ayurvedic medicine for its cognitive-enhancing and neuroprotective properties. Its key bioactive compounds, including celastrine and paniculatine, contribute to its pharmacological profile by enhancing cholinergic neurotransmission, inhibiting oxidative stress, and reducing inflammation. Both plants have demonstrated favorable safety profiles in preclinical studies, showing low toxicity at traditional dosages. Limited human studies report mild and transient side effects, supporting the traditional use of these plants. However, there remains a need for comprehensive clinical studies to confirm their safety and efficacy, particularly for long-term use and in special populations. This review highlights the pharmacological mechanisms, traditional uses, and safety profiles of Spermacoce latifolia and Celastrus paniculatus, emphasizing their potential as therapeutic agents. Future research should focus on detailed molecular studies and extensive clinical trials to fully explore their medicinal potential and ensure their safe application in modern medicine.