Abstract: Global warming impacts such as increasing carbon dioxide (CO₂) concentrations and effect of worsening local droughts on crop growth and yield are becoming progressively evident. Endophytic microbes form symbiotic relationships with host plants. Due to their long-term residence in a plant’s specialized environment, they play a crucial role in the growth, development, and stress resistance of crops. The symbiotic relationships between crops and endophytic microbes directly affect the response of crops to environmental changes. This article reviews the crop-endophyte symbiotic system and its regulation of crop physiological processes under CO₂ and drought stress. It discusses the diversity of endophytic microbial communities in crops, activation of host resistance, enhancement of tolerance to the environment, and antagonistic characteristics against pathogens. Specifically, endophytic microbes can help crops adapt to increased CO₂ concentrations and drought stress by enhancing the stomatal regulation ability of the host and increasing its root water and nutrient absorption capacity, thereby reducing the negative impact of environmental changes on crop growth and increasing crop yield. Additionally, endophytic microbes can activate the host defense system, enhance resistance to pathogens, and reduce the impact of diseases on crops. Future research should prioritize the response mechanisms of the crop-endophyte symbiotic system to increase CO₂ concentrations and compound stresses to enhance crop resistance to extreme environmental changes and provide new insights and strategies for crop breeding for stress resistance.