Changes in consumer lifestyles have raised awareness of a variety of food options and packaging technologies. Active and smart packaging is an innovative technology that serves to enhance the safety and quality of food products like fruit, vegetables, fish, and meat. Smart packaging, as a subset of this technology, entails the integration of additives into packaging materials, thereby facilitating the preservation or extension of product quality and shelf life. This technological approach stimulates a heightened demand for safer food products with a prolonged shelf life. Active packaging predominantly relies on the utilization of natural active substances. Therefore, the combination of active substances has a significant impact on the characteristics of active packaging, particularly on polymeric blends like polylactic acid (PLA) as a matrix. Therefore, this review will summarize how the addition of natural active agents influences the performance of smart packaging through systematic analysis, providing new insights into the types of active agents on physical–mechanical properties, colony reduction, and its application in foods. Through their integration, the market for active and smart packaging systems is expected to have a bright future.