Phytochemicals and antioxidant properties of red sweet pepper cv Topepo grown in soil amended with different organic fertilizers were compared with that grown in unamended soil. Organic fertilizers are an environmentally friendly alternative to recovery infertile soils that resulted from the intensified agricultural practices in red Topepo production. The aim was to discriminate the effects of organic fertilizers one from each other on the quality of red Topepo to find out the better sustainable fertilization practice for its cultivation. Results showed that compost from vegetable residues (CV) enhanced the synthesis of total phenols, flavonoids, ascorbic acid, vitamin E, carotenoids, anthocyanins, as well as carbohydrates, antioxidant activities, and aroma profiling, compared to horse manure (HD), compost from olive pomace (CO), and control (CTR). The results indicated a specificity between the quality of red Topepo and compost composition, highlighting that vegetable residues increased the synthesis of secondary metabolites, enhancing sustainably, the nutraceutical, sensorial, and economic value of red Topepo. The fertilizer composition resulted largely responsible for the synthesis of bioactive compounds, flavor, and aroma of this fruit.