Tryptophan decarboxylase (TDC), the rate-limiting enzyme of tryptophan metabolism in plants, is essential for the production of a series of bioactive molecules, such as serotonin, melatonin and the plant hormone indole-3-acetic acid and therefore plays crucial roles in various aspects of growth and development. However, its roles in determining wheat grain quality and stress resilience capacity remain unknown, limiting its utilisation in wheat improvement. In this study, we found that overexpression of AevTDC1 (AevTDC1-OX) of Aegilops variabilis, a wheat relative, did not significantly impair yield-related traits of wheat, but remarkably elevated the content of tryptamine, serotonin, melatonin and gamma-aminobutyric acid in the grains. Additionally, AevTDC1-OX simultaneously improved the defensive capabilities to cereal cyst nematode (CCN) and drought stress. Besides the known role in responding to CCN infection by regulating salicylic acid biosynthesis, we further found that AevTDC1-OX increased the expression of TaXTH23 and consequently enhanced cell wall thickness in the root. On the other hand, we observed significantly promoted ethylene biosynthesis in AevTDC1-OX wheat, which contributed to improved drought tolerance by controlling stomatal aperture. Moreover, TaWRKY65, upregulated by both AevTDC1-OX and drought stress, was unveiled to positively regulate drought tolerance. We proved that this function was achieved, at least partly, through directly modulating ethylene biosynthesis via promoting the expression of TaACS, a key ethylene biosynthesis gene. These results provide new knowledge on the essential roles of TDC in the functional quality of grains and the stress resilience capacity in wheat, revealing great potential for the manipulation of tryptophan metabolism for application in wheat genetic improvement.