Simple Summary This research highlights the prospect of kurugua seed by-product as a nutraceutical and functional food ingredient. Nutritional and bioactive profiling revealed that kurugua is rich in excellent nutritional compounds that can be exploited for human food development or in animal feed formulations. The seed by-product has shown great promise as an effective hepatoprotective agent and could be targeted for drug development. The "Kurugua" (Sicana odorifera) is a native fruit that demonstrates attractive nutritional, coloring, flavoring, and antioxidant properties. The main by-products from the processing and consumption of kurugua fruit are epicarp and seeds. In this work, the properties of the seeds of S. odorifera were evaluated. The nutritional composition of the fruit seeds was determined through AOAC official methods and UHPLC-ESI-MS/MS profiling. The antioxidant activities were determined using in vitro methods, and the acute toxicity and hepatoprotective properties were investigated in Swiss albino mice. Quercetin derivatives and cucurbitacins were the main phytochemicals in the seeds' methanolic extract and demonstrated some biological activities. GC-MS analysis revealed the essential fatty acids linolenic and linoleic as the main compounds present in seeds oil. The methanolic extract significantly reduced the serum levels of glutamic-pyruvic transaminase (GPT) and glutamic-oxaloacetic transaminase (GOT) in mice with induced hepatotoxicity (GPT p < 0.05; GOT p < 0.001) at the minor concentration tested (100 mg/kg EMSo). The results suggest that the S. odorifera seeds as by-products show potential use as a source of phytochemicals and in the production of oils with application in food supplements and nutraceuticals. Their integral use could contribute to waste reduction from kurugua fruits processing within the food safety and environmental sustainability framework.