The genus Calliandra (Leguminosae: Mimosoideae) encompasses over 200 species, many of which hold significant ethnobotanical value. However, a critical and comprehensive review consolidating their phytochemical and pharmacological knowledge is currently lacking. This article aims to provide a detailed and analytical overview of the traditional uses, phytochemistry, and pharmacological properties of the most studied Calliandra species, identifying trends, gaps, and future research priorities. A systematic literature search was conducted using Google Scholar, Scopus, Web of Science, and PubMed from 1986 to 2025. The review focuses on Calliandra portoricensis, Calliandra haematocephala, and Calliandra surinamensis due to the relative abundance of scientific literature concerning their medicinal applications. These species produce a diverse array of secondary metabolites, including distinctive galloylated flavonoids, phenolic acids, and triterpenes. Extracts and isolated compounds demonstrate a wide range of pharmacological activities, such as antioxidant, antimicrobial, anti-inflammatory, antidiabetic, and anticancer effects, providing a scientific basis for their traditional uses. The genus Calliandra represents a promising source of bioactive compounds. However, future research must focus on compound isolation, mechanistic studies, rigorous toxicological profiling, and clinical trials to fully realize its therapeutic potential.