The integrity of a package must be maintained by a material that can be heat sealed, particularly in medical, food, and pharmaceutical packaging applications. Obtaining an appropriate heat seal in packaging is crucial since, compared to package failure, heat seal failure is a more common reason for product degradation. Material selection and packaging methods should be evaluated carefully to choose the proper material that can effectively function under proper conditions. Hermetic seal property ensures the effectiveness of barrier layers in preventing oxygen permeation, loss of odor, and transmission of water vapor. Polylactic acid (PLA) is one of the biodegradable polymers with the greatest potential for heat sealing and thermal processing. To establish manufacturing protocols, verify seal effectiveness, and ensure product integrity, it is essential to consider the effects of controlling process parameters during package design. Therefore, to undercover the role of PLA structure on its properties, the factors impacting its heat-sealing feature are elaborated on in this chapter. Moreover, heat-sealing failures for PLA and PLA composite and different approaches to improve their heat-sealing strength are discussed. Finally, the application of the discussed concepts in food packaging is explored.