Drought stress (DS) negatively affects plant growth, productivity, and quality in semi-arid and arid regions. Nowadays, application of biofertilizers and stress-modulating nanoparticles (NPs) improves plant performance under stressful conditions. The study evaluated the impacts of arbuscular mycorrhizal fungi (Myco-Root) and TiO2 NPs on the nutrient uptake, dry yield, essential oil (EO) productivity, and EO quality of peppermint (Mentha piperita L.) under different irrigation regimes. The treatments included three irrigation regimes containing irrigation after 20% (I20, well-watered), 40% (I40, mild DS), and 60% (I60, severe DS) maximum allowable depletion (MAD) percentage of the soil’s available water as well as four fertilizer sources contain no fertilization (control), Myco-Root biofertilizer, TiO2 NPs, and an integrative application of Myco-Root + TiO2 NPs. The results demonstrated that the highest (195.72 g m−2) and the lowest dry yield (78.76 g m−2) of peppermint was obtained in well-watered conditions with integrative application of Myco-Root + TiO2 NPs and severe drought stress (I60) without fertilization, respectively. The dry yield of peppermint was reduced by 27.7 and 53.4% in mild (I40) and severe drought stress (I60), respectively. The maximum EO content (1.49%) and EO yield (2.30 g m−2) was recorded in mild drought stress (I40) treated with Myco-Root + TiO2 NPs. Based on the GC-MS and GC-FID analysis, 29 constituents were identified in peppermint EO, with the major constituents being menthol (38.99–52%), menthone (12.72–20.13%), 1,8-cineole (6.55–7.84%), and neo-menthol (3.14–4.52%), respectively. The maximum content of menthol, 1,8-cineole, and neo-menthol was obtained under mild drought stress (I40) fertilized with Myco-Root + TiO2 NPs. The results indicate that the integrative application of Myco-Root + TiO2 NPs could be used as an alternative method of using chemical fertilizers in sustainable agricultural systems for improving the EO quantity and