Despite being man-made, cyber-power systems and the associated cyber-attacks evolve in tandem with human expertise that matures over time. This dynamic mirrors the evolutionary processes observed in infectious disease ecology within microbial and human host systems. In this paper, we delve into the parallels between cyber-power systems and infectious disease ecology, culminating in the development of a bio-inspired cyber-immunity to enable cyber-resilient system. Parallels among these two systems are more evident with the digital automation of power system to enhance situational awareness and operational efficiency. However, automation has concurrently introduced multiple potential avenues for cyber attackers to exploit. Cyber adversaries are also advancing their methods, often leveraging intelligent algorithms and technologies to infiltrate confidential data, disrupt critical networks, and compromise communication channels similar to microbial. The data and system at risk are growing over time. Therefore, cyber resilience is the need of time, giving the power system utility the ability to anticipate, withstand, and recover from any cyber-attack. This work aims to develop a bio-inspired resilient cyber defense system to identify, protect, detect, respond, and recover from more complex and well-targeted cyber attacks. The proposed framework has two key features:(i) it draws upon principles and insights from engineered and natural defense mechanisms employed in combating infectious diseases, adapting them to bolster the cybersecurity of digital substation automation in energy systems, and ii) it constantly evolves in response to cyber attacks by transmitting iterative feedback to substation networks from each component at various stages of these attacks. This iterative learning process empowers the framework to safeguard against similar types of attacks in the future. Further we discuss the bio-inspired system’s ability to defend against cyber-attacks as well as iteratively improve through feedback learning from framework components for future attacks of a similar sort was further discussed. A realistic cyber attack use case scenario has been developed using a real-time cyber-power substation automation testbed to validate the proposed framework and demonstrate its potential future adoptions. With the implementation of this framework, cyber-power systems will be able to deal with randomness, ambiguity, and the rapid advancement of potential cyber threats while applying digital substation automation technologies. With the development of more intelligent technologies that can deal with incompleteness and uncertainty better than ever before, modern cyber defense systems can mimic immunity and resilience inspired by infectious disease ecology and natural host defense systems.