Nowadays, many types of research are looking for natural products to be used in several applications, particularly in the medical field. Psidium guajava Leave Extract was therefore used to impart multi-functional properties to cotton fabrics, such as antibacterial and antioxidant properties, in addition to ultraviolet protection. Two solvents have been used for the preparation of the extract, namely water, and ethanol. Both prepared extracts were used as a reducing and stabilizing agent in the synthesis of silver nanoparticles. Prepared extracts and synthesized nanoparticles have been characterized using a variety of techniques, such as total phenol content, antioxidant activity, particle size, FTIR, and TEM, and these techniques provide the extraction and synthesis of silver nanoparticles. The optimization of the treatment condition of cotton fabrics was evaluated at different concentrations, pH, time, and temperature. The assessment shows that the optimum condition for the treated cotton fabric has been achieved by using 100% of the extract at pH 8 for 15 min at 70°C. Monitoring was assessed as a UPF value. Antimicrobial results for treated tissues showed that Gram-negative bacteria showed less sensitivity to both extracts than Gram-positive bacteria, while fungal strains showed high sensitivity to both extracts. The antioxidant properties of the treated fabrics may also improve, allowing them to be considered in medical applications.