Edible polymers such as polysaccharides, proteins, and lipids are biodegradable and biocompatible materials applied as a thin layer to the surface of food or inside the package. They enhance food quality by prolonging its shelf-life and avoiding the deterioration phenomena caused by oxidation, humidity, and microbial activity. In order to improve the biopolymer performance, antimicrobial agents and plasticizers are also included in the formulation of the main compounds utilized for edible coating packages. Secondary natural compounds (SC) are molecules not essential for growth produced by some plants, fungi, and microorganisms. SC derived from plants and fungi have attracted much attention in the food packaging industry because of their natural antimicrobial and antioxidant activities and their effect on the biofilm’s mechanical properties. The antimicrobial and antioxidant activities inhibit pathogenic microorganism growth and protect food from oxidation. Furthermore, based on the biopolymer and SC used in the formulation, their specific mass ratio, the peculiar physical interaction occurring between their functional groups, and the experimental procedure adopted for edible coating preparation, the final properties as mechanical resistance and gas barrier properties can be opportunely modulated. This review summarizes the investigations on the antimicrobial, mechanical, and barrier properties of the secondary natural compounds employed in edible biopolymer-based systems used for food packaging materials.