Fresh-cut cantaloupe is very perishable due to the mechanical damage and susceptibility to microorganism infections, which limit their shelf life. Cantaloupe is a popular fruit with high moisture content and nutritional value. This study aimed to enhance fresh-cut cantaloupe quality and extend the shelf life by employing soy protein isolates (SPI) coating solutions containing calcium lactate (CaL) and λ-aminobutyric acid (GABA). Cold plasma (CP) was used to augment the antioxidant and antimicrobial activities of the coatings. The coatings were meticulously characterized, and their impact on fresh-cut cantaloupe was assessed through physicochemical and microbiological parameters. The incorporation of CaL and GABA and the CP treatment heightened the antioxidant activity of the SPI coating, resulting in a substantial increase in DPPH and ABTS free radical scavenging activities by 58% and 30%, respectively. Application of the composite coating included a noteworthy 24% reduction in water loss on fresh-cut cantaloupe, maintaining color stability and total soluble solids content. Moreover, the treatment of composite coating effectively controlled microbial growth, ensuring fresh-cut cantaloupe remained in an edible state at the conclusion of the storage period. The coating treatment has extended the shelf life of fresh-cut cantaloupe from 6 d to 10 d at 0 °C. In conclusion, the CP-treated bioactive coating containing CaL and GABA prolonged the shelf life, enhanced nutritional value, and preserved the microbial quality attributes of fresh-cut cantaloupe.