The trend of global warming is becoming increasingly evident, with frequent extreme high-temperature events posing a severe challenge to food security. Rice (Oryza sativa L.), the world's primary food crop, is highly susceptible to the adverse effects of high-temperature stress throughout its growth cycle. High temperatures, defined as ambient temperatures exceeding 35 degrees C during reproductive stages and 33 degrees C during vegetative stages, can impair seed germination, reduce tillering, disrupt pollination, and diminish grain quality. Notably, heat stress during the grain-filling stage accelerates grain maturation, leading to increased chalkiness, a higher degree of chalky formation, deteriorated cooking and eating quality, and decreased grain weight. To cope with high-temperature stress, rice activates a series of complex physiological and biochemical responses, including heat-related signaling pathways and transcriptional regulatory networks. Although some agronomic practices and genetic improvement methods have been developed to enhance rice's heat tolerance, the regulatory mechanisms of rice's response to high-temperature stress, especially the molecular mechanisms during the grain-filling stage, remain poorly understood. This review identifies knowledge gaps in understanding rice's response mechanisms, emphasizing molecular pathways during the grain-filling stage and provides an outlook on future rice high-temperature defense measures.