Huanglongbing (HLB), a.k.a. citrus greening, is an endemic disease significantly impacting Florida and Texas citrus production. HLB-affected trees are compromised in the canopy and root health, often found with heavy loss of root mass that impairs water and nutrient uptake, leading to nutrient deficiencies. The prevalent presence of the suspected causal organism of HLB, Candidatus Liberibacter asiaticus (CLas) bacterium, in the citrus phloem leads to a cascade of active defense responses triggered by plant-pathogen interactions. One of the crucial outcomes of the interactions is the production of reactive oxygen species, leading to excessive oxidative stress that, over time, weakens tree health. Therefore, this research investigated the therapeutic strategies to mitigate nutrient deficiencies and HLB symptoms, attenuate reactive oxygen species load, and improve the production of premium grapefruits in trees affected by HLB by combining an integrated approach of micronutrient applications with antioxidants. The experiment design consisted of the foliar application of micronutrients, zinc (Zn), iron (Fe), and manganese (Mn) varied in two rates: 2 quarts/acre (control) and 3 quarts/acre that were conducted alone or in combination with gamma-aminobutyric acid (GABA), uric acid, and gibberellic acid (GA). The micronutrients, GABA, and uric acid applications were conducted at an interval of three months, while GA sprays were limited between blooming to the pre-harvest period in the HLB-affected mature grapefruit grove with a tree density of 104 trees/acre in the Lower Rio Grande Valley of Texas. The results demonstrated that merely increasing micronutrient application to 3 quarts/acre improved canopy health, with healthy (non-HLB-symptomatic) canopy quadrants reaching an average of 30% compared to 16.7% in the control treatment. Moreover, the standalone 3-quarts/acre significantly improved the yield of premium-size grapefruit to 25% compared to 6.2% in 2-quarts/acre only. The combination of GA (10 Fl.Oz/acre) and GABA (8 gm/tree) with control micronutrient treatment enhanced healthy canopy quadrants to 33% and 38%, respectively, compared to 19% in the micronutrient-only control. In 3 quarts/acre, GA and GABA showed synergistic effects in improving the canopy health by alleviating HLB severity. This applied research provides a practical framework for translating laboratory findings into field applications for managing HLB-affected trees. The integrated approach of combining enhanced micronutrient applications with antioxidants and phytohormones shows promise in mitigating HLB symptoms and improving fruit yield, particularly in the premium size category.