Abstract <p>Drought is one of the most critical abiotic stresses limiting crop productivity by disrupting cellular water balance, inducing oxidative stress, and impairing photosynthetic metabolism. In rice (<i>Oryza sativa</i> L.), drought triggers a cascade of physiological and biochemical adjustments that determine genotypic resilience, including enhanced antioxidant activity, osmotic regulation, and membrane protection. To elucidate these adaptive mechanisms, a core set of 16 rice genotypes was developed from an initial panel of 150 accessions, representing maximum physiological and biochemical diversity. These genotypes were evaluated under drought and irrigated conditions for key traits such as relative water content (RWC), membrane stability index (MSI), nitrate reductase (NR) activity, peroxidase (POD), catalase (CAT), superoxide dismutase (SOD), proline (PRO), SPAD chlorophyll index, and yield. Significant genotypic variation was observed across all traits. Correlation analysis revealed that yield under drought was positively associated with SOD, MSI, and RWC, highlighting the critical role of antioxidant defense and cellular water retention in sustaining photosynthetic function. Principal component analysis (PCA) efficiently captured the multidimensional variation among genotypes, while the Multi-Trait Genotype–Ideotype Distance Index (MGIDI) enabled integrated selection for physiological and biochemical efficiency. Genotype 5(RL-5750), 6(RL-9815) and 4(RL-4499) exhibited superior adaptive responses under drought, whereas genotype 1(RL-671), 3(RL-2503) and 2(RL-1682) performed best under irrigation. This integrative physiological framework demonstrates that drought tolerance in rice is governed by coordinated antioxidant regulation, membrane stability, and tissue hydration. The findings provide a mechanistic basis for identifying physiological markers and elite genotypes, offering valuable resources for breeding programs aimed at improving drought resilience and yield stability in rice.</p>