Cucumis metuliferus E. Meyer ex Naudin belongs to the family Cucurbitaceae. It is an annual vegetable species known as horned melon or kiwano. Fruits are recommended for the daily diet because they provide vitamins, minerals, and phytochemicals to alleviate malnutrition and improve human health. In this study, kiwano was cultivated in the climatic conditions of Southwestern Romania, which is characterized by warm summers, lower precipitation, and high temperatures, ensuring optimal conditions for growth and development. The fruits were harvested at three stages of consumption: immature stage (green), intermediate stage (white–yellow) or the mature stage (yellow–orange). They were also subjected to analysis on the productive yield and physical–chemical properties. The results showed that the number of fruits ranged from 13.9 to 15.3 fruits/plant, and their average weight had values from 204 g to 234 g, depending on the harvest stage. The results obtained for bioactive compounds and antioxidant activity indicated significant differences (p ≤ 0.05), depending on the harvesting stage. The highest values for the antioxidant capacity (140.90 μM TE/100g DPPH) and total polyphenols (48.78 TPC mg/100 g) were recorded in the immature fruit phase, as well as for the carbohydrate content (3.56%), total protein (1.98%), ascorbic acid (4.3 mg/100 g f.w.), and carotene (0.98 mg/100 g) in the mature fruit phase. These results may stimulate interest in the introduction of this species as a niche crop and for consumption as a source of natural antioxidants for the prevention of diseases due to oxidative stress.