For commercial leather processing, chrome tanning is the most used approach but it significantly contributes to environmental pollution. Vegetable tannins, which are large polyphenolic compounds, form strong interactions with proteins and carbohydrates, thereby enhancing the adaptability and value of vegetable-tanned leather as well as reducing environmental impact. In this study, vegetable tannins were extracted from the leaves of Guava plants (Psidium guajava) using ethanol as the solvent, facilitated by ultrasound. Extracted tannins were quantified using the Folin–Ciocâlteu reagent with ultraviolet-visible spectroscopic method. Ultrasound enhanced the extraction process producing a high yield in less time due to its mechanical, thermal, and cavitation impacts. The extracted tannins were characterized by a variety of spectroscopic techniques, including Proton (1H) Nuclear magnetic resonance, Fourier-transform infrared, and ultraviolet-visible spectroscopy. The effect of various process variables, such as temperature, solid-liquid ratio, ultrasonic power, extraction period, and powder fineness, were also investigated to optimize the extraction process. Finally, the extracted tannins were employed in leather tanning processes to assess their potential as tanning agents. The extracted tannins ensured uniform diffusion of tannins, improved thermal stability and reduced the number of tannins in effluent by 68% making it an environmentally friendly leather tanning process.