In this study, an eco-friendly strategy for the surface modification and multifunctionalization of denim fabric is successfully developed by N2 or air atmospheric plasma pretreatment followed by Post-treatment with environmentally sound active ingredients, namely aloe vera, neem, cinnamon, vanillin, ZnO nanoparticles, SiO2 nanoparticles, ascorbic acid, and salicylic acid, both individually and in combination. The change in surface morphology and the imparted antibacterial properties, UV resistance, hydrophobicity, and scent emission, along with coloration and durability to wash, are evaluated. A combination of plasma treatment and subsequent functional finishes result in a remarkable improvement in the imparted functional properties along with a variation in the color properties. The variations in the imparted functional and color properties are governed by the type of plasma gas and functional additive. The imparted functional properties are still high, even after 10 washing cycles. The mode of interaction between the modified substrate and the functional materials applied is also discussed.