Citrus production is a major agro-industrial activity worldwide, generating large amounts of by-products during juice processing. Food Machinery Corporation (FMC) technology enables the simultaneous extraction of juice and essential oils, generating an orange residue after essential oil extraction (OER) whose composition may differ from that of the original orange residue (OR). This study evaluated the effect of industrial essential oil extraction on the bioactive properties and lipophilic composition of Navel orange residues. OR and OER by-products were freeze-dried and milled, yielding dried powders designated as DOR and DOER, respectively. Total phenolic content (TPC), total flavonoids, carotenoids, and antioxidant activity (ABTS and ORAC-FL assays) were determined. Oil extraction yield was determined, and the tocopherol profile was evaluated by chromatographic analysis. DOR showed higher contents of TPC (12.8 ± 1.1 vs. 10.5 ± 0.2 mg GAE/g), total flavonoids (0.97 ± 0.01 vs. 0.74 ± 0.01 mg quercetin equivalents/g), and carotenoids (129.2 ± 1.9 vs. 74.05 ± 0.02 μg/g) than DOER. However, ORAC-FL values were significantly higher in DOER (212.0 ± 5.6 µmol TE/g) than in DOR (172.1 ± 5.6 µmol TE/g), whereas no significant differences were observed by ABTS. These findings suggest that antioxidant activity depends not only on the concentration of bioactive compounds but also on their availability and interactions within the food matrix. FMC processing reduced total tocopherol content by approximately 65%, from 276.5 ± 0.4 to 97.0 ± 0.5 mg/kg of residue. α-Tocopherol was the most affected homologue, decreasing from 186.2 to 50.5 mg/kg of residue (≈73% reduction), whereas β+γ-tocopherols showed a lower decrease. This differential behavior resulted in a reduction of the α/(β+γ) ratio from 2.1 to 1.1. These results demonstrate that FMC essential oil extraction significantly modifies the bioactive and lipophilic composition of orange residues, while preserving or enhancing specific antioxidant properties, highlighting their potential as sustainable functional ingredients.