The present study examined the synergistic impact of exogenous hydrogen sulfide (H2S) and nitric oxide (NO) in mitigating nickel (Ni; 1 mu M) induced toxicity in two paddy field cyanobacteria, namely Nostoc muscorum ATCC 27893 and Anabaena sp. PCC 7120. The evaluation encompasses growth, photosynthetic pigments (chlorophyll a, carotenoids and phycocyanin), oxidative biomarkers, and enzymes and metabolites involved in the ascorbate-glutathione (AsA-GSH) cycle. Cellular Ni accumulation resulted in elevated reactive oxygen species (ROS) production, reduced pigment levels, and impeded growth. The augmented activities of AsA-GSH cycle enzymes (ascorbate peroxidase, glutathione reductase, and dehydroascorbate reductase) were unable to counteract these toxic effects. However, exogenous supplementation of 8 mu M H2S and 10 mu M NO significantly reduced Ni-induced toxicity. This amelioration involved decreasing ROS levels, minimizing cellular Ni accumulation, enhancing photosynthetic pigments level, and elevating the AsA-GSH cycle's potential, thereby functioning as promoters of the metal detoxification system. The SEM analysis depicted Ni-accumulation on the surface of both cyanobacterial cells. Furthermore, introducing scavengers (PTIO for NO and HT for H2S) and inhibitors (L-NAME for NO and PAG for H2S) reversed the positive effects of H2S and NO, exacerbating damages under Ni-induced stress. This study proposed a cross-talk mechanism between H2S and NO, wherein H2S downregulates signaling on NO-mediated alleviation under Ni stress in both cyanobacteria. Additionally, the present work suggests that utilizing a lower dose of H2S and NO (cost-effective) in paddy fields could enhance the growth of cyanobacteria (as a significant biofertilizer), even under existing stressful conditions. This approach aims to support sustainable agriculture and uphold rice crop productivity.