Gain-of-function mutations in SHP-2/PTPN11 cause Noonan syndrome, a human developmental disorder. Noonan syndrome is characterized by proportionate short stature, facial dysmorphia, increased risk of leukemia, and congenital heart defects in ≈50% of cases. Congenital heart abnormalities are common in Noonan syndrome, but the signaling pathway(s) linking gain-of-function SHP-2 mutants to heart disease is unclear. Diverse cell types coordinate cardiac morphogenesis, which is regulated by calcium (Ca²⁺) and the nuclear factor of activated T-cells (NFAT). It has been shown that the frequency of Ca²⁺ oscillations regulates NFAT activity. Here, we show that in fibroblasts, Ca²⁺ oscillations in response to FGF-2 require the phosphatase activity of SHP-2. Conversely, gain-of-function mutants of SHP-2 enhanced FGF-2-mediated Ca²⁺ oscillations in fibroblasts and spontaneous Ca²⁺ oscillations in cardiomyocytes. The enhanced frequency of cardiomyocyte Ca²⁺ oscillations induced by a gain-of-function SHP-2 mutant correlated with reduced nuclear translocation and transcriptional activity of NFAT. These data imply that gain-of-function SHP-2 mutants disrupt the Ca²⁺ oscillatory control of NFAT, suggesting a potential mechanism for congenital heart defects in Noonan syndrome.