Nowadays, the application of nanoparticles as a novel elicitor has been studied from various aspects, including possible enhancement of the production of different secondary metabolites and endogenous antioxidant properties of medicinal plants. The objective of this work was to evaluate the foliar application of titanium dioxide nanoparticles (TiO2 NPs) on the growth, some physiological traits, and in particular, the content of different groups of phenolic compounds (i.e., the total phenol content, ortho-diphenols, phenolic acids, flavonoids, and proanthocyanidin), and the antioxidant capacity of Ziziphora clinopodioides Lam. at two harvest time. Three-month-old plants were foliar sprayed with 10, 60 and 120 mg/L TiO2 NPs and harvested at two time points (T1 = 7 d and T2 = 14 d after elicitation). Although 60 mg/L TiO2 NPs caused the maximum value for the length and weight of aerial parts and roots as well as the contents of chlorophyll a, chlorophyll b, and carotenoids at 14 d after foliar-applied nanoparticles, the highest chlorophyll a/b ratio was recorded under 10 mg/L TiO2 NPs treatment at both harvest time. With the higher content of all phenolic derivatives at the second harvest time in comparison to the first one, 60 mg/L TiO2 NPs was found to be optimum in creating the maximum accumulation of phenolic and flavonoid composition with the respective average values of 1.261 ± 0.15mg/g fr wt and 1.04 ±0.13 mg/g fr wt. A strong correlation between antioxidant activity (TAC, DPPH, and FRAP values) and enhanced phenolic compounds of NP-elicited plants was noticeable. Due to the increased phenolic compositions and antioxidant activity of Z. clinopodioides, it could be assumed that the use of TiO2 NPs enhances the medicinal value of Ziziphora. However, TiO2 NPs inhibitory impact at high concentrations should not be neglected.

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