This study examined how combining curry leaf (Murraya koenigii) and marigold leaf (Tagetes erecta) extracts affects immune response and disease resistance in Labeo rohita (rohu) fish against Saprolegnia parasitica infection. We conducted a 74-day trial using 360 juvenile rohu divided into four treatment groups: control (T0), curry leaf extract (T1), marigold leaf extract (T2), and combined extracts (T3). The trial consisted of a 60-day feeding period followed by a 14-day pathogen challenge test. The combined extract treatment (T3) demonstrated superior results across all measured parameters. Fish in T3 showed significantly enhanced hematological values, with the highest hemoglobin content (9.4 ± 0.5 g/dL) and total leukocyte count (41.3 ± 2.5 × 103/μL) post-challenge. Immunological parameters were markedly elevated in T3, with serum immunoglobulin levels reaching 22.7 ± 1.3 mg/mL after pathogen exposure. Importantly, liver enzyme levels remained stable across all treatments, indicating the safety of the extracts. Disease resistance metrics in T3 were notably superior, with the highest survival rate (86.7%), minimal lesion severity (1.2 ± 0.2 on a 4-point scale), and lowest fungal load (1.8 × 103 ± 0.3 × 103 gene copies/mg tissue) following pathogen challenge. The enhanced performance of the combined treatment suggests a synergistic effect, potentially activating multiple immune pathways simultaneously. These findings demonstrate that the combination of curry and marigold leaf extracts offers a promising natural approach for enhancing disease resistance in aquaculture.