Physiological, nutritional, and metabolomic responses of wheat (Triticum aestivum) plants to two surfactants (SAs) (nonylphenoxy polyethoxy ethanol at 1 g/L�"Nonionic SA" versus a combination of 0.5 g/L xanthan gum and 5 g/L triethyl citrate�"Green SA") were investigated at two application stages and three plant response times (e.g., day 2, day 4, and day 8). The concentration was based on the manufacturer's recommendation. Although dry biomass and mineral nutrients remained unchanged for most experimental conditions, metabolomics revealed changes in plant internal status. When the Green SA was applied at the early tillering stage (ET, day 21), cysteine and methionine metabolism was consistently perturbed for all three plant response times. However, metabolite reprogramming faded rapidly by day 8, with only one significantly altered amino acid (aspartic acid) detected. On the contrary, when SAs were applied at the flag leaf stage (FL, day 32), the maximum perturbation of metabolomic pathways (10 pathways perturbed for Green SA and 8 for Nonionic SA) occurred on day 8 with a significant perturbation of the tricarboxylic acid cycle for both SAs. Furthermore, Green SA applied at FL disturbed more metabolomic pathways and almost two times more metabolites (19 vs 10) that were positively correlated to the plant response time than Nonionic SA. That indicated Green SA applied at FL resulted in a more profound impact on the plant defense system and nitrogen and carbon metabolism, mostly increasing the levels of perturbed metabolites by 1.1-to 2.0-fold changes. Determining the molecular response of plants after SA application can serve to better design targeted delivery of nutrients or active ingredients onto superhydrophobic leaf surfaces.