Alzheimer's disease (AD) is the most common cause of dementia, characterized by amyloid-β (Aβ42) accumulation, with a progressive breakdown of synapsis connection, neuronal death, and cognitive loss. Mitochondrial impairment emerges early in AD, preceding cognitive symptoms and contributing to disease progression. Vitamin D (VD) is a neurosteroid that acts as a transcription factor through its nuclear receptor, the vitamin D receptor (VDR), playing a central role in metabolic control. The Drosophila VDR ortholog, hormone receptor 96 (Hr96), is known to regulate xenobiotic protection and energy metabolism, but its neuronal functions and impact on AD pathomechanisms are poorly understood. Here, we investigate Hr96's role in neuronal and mitochondrial homeostasis, hypothesizing that its signaling modulates mitochondrial dynamics and mitigates neurodegeneration in AD. We identified Hr96-regulated genes involved in lipid metabolism, oxidative stress, and mitochondrial dynamics. Modulation of Hr96 expression in fly neurons revealed that knockdown had minimal early effects but led to reduced lifespan and motor decline, while overexpression induced metabolic imbalances, circadian disruptions, and premature mortality. Mitochondrial analyses showed that Hr96 overexpression affected functionality, increased fragmentation, and upregulated fission markers, such as Drp1, suggesting a role in mitochondrial dynamics. Then, when we studied an AD fly model, Hr96 loss exacerbated Aβ42-induced neurotoxicity, reducing lifespan and motor performance. Conversely, Hr96 overexpression extended lifespan under Aβ42 toxicity but did not affect neuromuscular junction bouton number and size. Furthermore, when mitochondrial parameters were analyzed, overexpression of this gene suppresses Aβ42-linked mitochondrial phenotypes to levels closer to wild type. These findings unveil Hr96 as a potential modulator of mitochondrial and neuronal homeostasis, and that in the context of a time-dependent insult such as Aβ42 accumulation, its overexpression is protective. Further studies are needed to elucidate its role in mitochondrial regulation and transcriptional networks, paving the way for therapeutic strategies targeting mitochondrial dysfunction in neurodegeneration.