Gallium (Ga) and indium (In) are extensively used in the semiconductor industry in current days, and are both emerging contamination elements to our environment. Due to the limited information known about Ga and In contaminants, previous research has evaluated their possible risk and toxicity to rice seedlings. It was surprised to observe a differential physiological response to Ga and In: the beneficial effect on the growth of rice seedlings was found while applying low Ga concentrations (less than 10 ppm); on the contrary, the In treated seedlings (higher than 0.08ppm) displayed growth inhibition, such as shorter root length. To elucidate their difference on the regulatory mechanism, this study first compared the gene expression between Ga- or In- treated plants using whole transcriptome shotgun sequencing (RNA-sequencing). Differential expression was observed in the functional genes related to ion uptake, reactive oxygen species (ROS) scavenging, and stress response. Their changes at the molecular level was further correlated to physiological parameters, e.g. the photosynthesis efficiency and the H₂O₂ distribution, and the ROS scavenging enzyme activity. Our finding provides information on the differential molecular regulation and distinguishing physiological response to Ga and In stress in rice seedlings.