This study investigated the proximate, mineral, and microbial composition of Nile tilapia preserved using three different salting methods: Kench, Brining, and Granulated Salting. A total of 27 fish samples were processed, with 9 fish allocated to each preservation method. The results of the proximate composition analysis revealed that Brining resulted in the highest moisture content (52.60%) compared to Kench (45.23%) and Granulated Salting (40.10%) (p < 0.05). Granulated Salting produced the highest crude protein content (32.40%), which was significantly greater than that of Brining (28.47%) and Kench (30.30%). While Brining exhibited the highest crude fat content (9.20%) (p < 0.05), Granulated Salting had the highest ash (15.77%) and pH (6.47) values, indicating its effectiveness in preserving fish quality. The mineral composition analysis showed significant differences among the methods, with Granulated Salting having the highest sodium (3500.00 mg) and calcium (200.00 mg) contents (p < 0.05). The microbial analysis indicated that Kench had the highest bacterial and fungal counts, with a significant presence of pathogens such as S. aureus and P. aeruginosa. In contrast, Granulated Salting exhibited the lowest microbial load, significantly reducing bacterial and fungal contamination (p < 0.05). In conclusion, Granulated Salting emerged as the most effective method for preserving the nutritional and microbiological quality of Nile tilapia. It demonstrated superior efficacy in reducing moisture content, preserving protein, minimizing lipid oxidation, and controlling microbial growth. Therefore, Granulated Salting is recommended as the preferred method for preserving Nile tilapia due to its exceptional ability to retain protein content, maintain biochemical stability, and effectively reduce microbial contamination.