The production of smokeable tobacco for use in cigarettes is characterized by the production of pre-harvest and post-harvest waste, with ensuing undesirable effects on the environment. The inflorescences of tobacco after blunting, deflowering, or topping are considered pre-harvest waste and left in the field. Using green and ecofriendly solvents such as Natural deep eutectic solvents (NaDESs), these wastes could be used to obtain antioxidant molecules of interest in cosmetics. Taking into account its potential as plant matrix to obtain metabolites of commercial interest, tobacco inflorescences and inflorescence powders of different particle sizes were characterized by optic and electronic microscopy. Thus, the powdered inflorescences were extracted with four conventional solvents, i.e., distilled water (DW), acetone: distilled water (AW), ethanol 70° (EW), methanol (Me), and five NaDESs, i.e., lactic acid: sucrose (LAS), lactic acid: sucrose: distilled water (SALA), fructose: glucose: sucrose: distilled water (FGS), choline chloride: urea: distilled water (CU), and citric acid: propylene glycol (CAP). Among the tested NADESs, SALA was the most promising solvent; higher extraction yields of total phenolic compound (3420.0 ± 9.4 µg GAE/mL) than conventional solvents were attained and it was the only selective solvent to phenolics. CU was the best solvent for flavonoids and alkaloids extraction (215.3 ± 3.2 µg QE/mL and 392.3 ± 8.0 µg ACE/mL, respectively). All extracts showed antioxidant activity. A heatmap with dendrogram and main component analysis showed that acid-based NaDESs are grouped together, this group being the one with the best performance in H2O2 scavenging. The extracts obtained with green solvents could be used directly in cosmetic formulations as antioxidant ingredients because both tobacco flower oil and flower extracts are listed in the cosmetic ingredients database as non-toxic products. Additionally, the demand for sustainable ecological cosmetics is growing. In this sense, NaDESs represent an opportunity to develop innovative extracts with unique phytochemical fingerprints and biological activities.