During two-line hybrid rice seed production, thermo-sensitive genic male sterile (TGMS) rice lines are susceptible to low temperature, leading to fertility alteration (from sterile to fertile) and production of false hybrids (self-pollination). To explore appropriate solutions to reduce the chance of seed production failure, two exogenous substances, d-Arg and ethephon, were applied to restrain the fertility alteration induced by low temperature (22.0 °C), respectively. The fertile pollen grains and bagged seed setting rate of TGMS rice line Jing 4155S (with the critical fertility/sterility alteration temperature of 23.5 °C) under low temperature could be reduced to 0% by spraying exogenous substances. Transcriptome analysis of young panicles of TGMS rice line Jing 4155S demonstrated that the expressions of multiple transcription factors (MYB, FAR1, and ERF, etc.) changed, and hence affecting various downstream related genes and metabolic processes, including hormonal signal transduction, plant pathogen interactions, circadian rhythm pathway, carbohydrate metabolism, cell wall synthesis, and lipid metabolism, etc. The enhanced ethylene biosynthesis and the prevented redox equilibrium from unbalance to balance in young panicles were one of the major reasons that fertility alteration was inhibited by exogenous substances. Our results made a contribution to the solution for inhibiting fertility alteration induced by low temperature in two-line TGMS rice lines during hybrid seed production.