Present investigation reports the role of calcium (Ca2+) and hydrogen sulfide (H2S) crosstalk associated with Vigna radiata seedlings subjected to K+ deficient conditions under short-term (24 h) and long-term (72 h) NaCl stress. Perusal of the data reveals that under short-term NaCl stress an initial decline in K+ level led to the elevation in Ca2+ and H2S levels along with improvement in antioxidant system and reduction in reactive oxygen species (ROS) production. Under long-term NaCl stress a further decline in K+ content was deleterious that led to a lower K+/Na+ ratio. This was followed by reduction in antioxidant system along with excessive accumulation of ROS and methylglyoxal content, and increased membrane damage. However, supplementation of the seedling roots with Ca2+ enhanced biosynthesis of H2S through enhancing cysteine pool. The present findings suggest that synergistic action of Ca2+ and H2S induced the activity of H+ -ATPase that created H+ gradient which in turn induced Na+/H+ antiport system that accelerated K+ influx and Na+ efflux. All of these together contributed to a higher K+/Na+ ratio, activation of antioxidative defense system, and maintenance of redox homeostasis and membrane integrity in Ca2+-supplemented stressed seedlings. Role of Ca2+ and H2S in the regulation of Na+/H+ antiport system was validated by the use of sodium orthovanadate (plasma membrane H+-ATPase inhibitor), tetraethylammonium chloride (K+ channel blocker), and amiloride (Na+/H+ antiporter inhibitor). Application of Ca2+-chelator EGTA (ethylene glycol-bis(b-aminoethylether)-N,N,N;N'-tetraacetic acid) and H2S scavenger hypotaurine abolished the effect of Ca2+, suggesting the involvement of Ca2+ and H2S in the alleviation of NaCl stress. Moreover, use of EGTA and HT also substantiates the downstream functioning of H2S during Ca2+-|mediated regulation of plant adaptive responses to NaCl stress. To sum up, present findings reveal the association of Ca2+ and H2S signaling in the regulation of ion homeostasis and antioxidant defense during K+-deficient NaCl stress.