Stryphnodendron adstringens (Martius) Coville is a medicinal plant described as having pharmacological properties as anti-inflammatory and antimicrobial activities. Silver chloride nanoparticles (AgCl-NPs) have shown great potential for biomedical applications with efficient antimicrobial properties. Here, we report the photosynthesis of AgCl-NPs using plant extract from S. adstringens (SaAgCl-NPs) and their cytotoxic and antimicrobial activities. We photosynthesized SaAgCl-NPs nearly spherical with low heterogeneity in size and enveloped by an organic material layer responsible for colloidal stability. SaAgCl-NPs was non-cytotoxic against mammalian VERO cells; however, SaAgCl-NPs presented remarkable antifungal activity against the pathogenic yeast Cryptococcus neoformans (MIC80 of 0.32 µg/mL) the causative agent of human cryptococcosis. Notable antibacterial activity was observed against Gram-negative bacteria Pseudomonas aeruginosa (MIC80 of 2.56 µg/mL) e Serratia marcescens (MIC80 of 20.48 µg/mL) both microorganisms associated with a variety of human infections, in particular pneumonia. In contrast, Gram-positive bacteria Staphylococcus aureus and Staphylococcus epidermidis, microorganisms that cause pathologies as skin infections, were less susceptible to the SaAgCl-NPs both with MIC80 of 40.93 µg/mL. Thus, SaAgCl-NPs represents an organic–inorganic hybrid nanomaterial with very low cytotoxicity against mammalian cells and high antimicrobial efficiency against pathogenic microorganisms and may be explored as an alternative to antimicrobial drugs. [ABSTRACT FROM AUTHOR]