Salinity, a severe worldwide issue, compromises the economic production of medicinal plants including mints and
causes drug-yield decline. γ-Aminobutyric acid (GABA) is a tolerance-inducing signaling bio-molecule in various plant
physiological processes. Pineapple mint (Mentha suaveolens Ehrh.) is a valuable medicinal herb with an exhilarating
scent of citrus fruit. Piperitenone oxide is the major bioactive constituent of its essential oil, having signifcant demand
by pharmaceutical industries. Nonetheless, modeling and optimizing the efective concentration of GABA remain
within twin foci of interest. Therefore, a two factor-fve level (NaCl 0-150 mM and GABA 0-2.4 mM) central composite
design was conducted to model and optimize drug yield and physiological responses of M. suaveolens. Based on the
design of experiments (DoE) approach, diferent linear, quadratic, cubic, and quartic models were assigned to the
response variables. Change trends of shoot and root dry weights followed a simple linear model, whereas sophisticated models (i.e., multiple polynomial regression) were ftted to the other traits. NaCl stress inevitably reduced root
and shoot dry weight, piperitenone oxide content, relative water content, pigments content, and maximum quantum
yield of PSII. However, content of malondialdehyde (MDA) and total favonoid, and DPPH radical scavenging activity were increased under salinity. Under severe NaCl stress (150 mM), the essential oil content (0.53%) was increased
three times in comparison with control (0.18%). Optimization analysis demonstrated that the highest amount of
essential oil (0.6%) and piperitenone oxide (81%) as a drug yield-determining component would be achievable by
application of 0.1–0.2 mM GABA under 100 mM NaCl. The highest dry weight of root and shoot was predicted to be
achieved at 2.4 mM GABA. Overall, extremely severe NaCl stress (i.e., more than 100 mM) in which a sharp drop in yield
components value was observed seemed to be out of M. sua