This study investigated the effects of coenzyme Q10 (CoQ10) administration on fibromyalgia (FM) symptoms and cognitive functions in a reserpine-induced FM model. It is also aimed to evaluate the role of the PGC-1α/FNDC5/BDNF pathway and oxidative stress in this process. Female Wistar rats were randomly assigned to control, FM, CoQ10, and FM + CoQ10 groups. The FM groups received daily subcutaneous reserpine (1 mg kg−1) for three consecutive days. The CoQ10 groups were administered 150 mg kg−1 of oral CoQ10 for 7 days. Behavioral and sensory assessments were conducted on days 0, 4, and 6. Mechanical allodynia was measured with the Von Frey test, while depressive-like behavior was assessed using the forced swim test. Locomotor activity and anxiety levels were evaluated via the elevated plus maze, and learning/memory performance were tested using the Morris water maze probe test. Reserpine exposure led to increased mechanical allodynia, decreased locomotor activity, elevated anxiety levels, increased depressive-like behavior, and impaired learning/memory (p < 0.05). These behavioral abnormalities were accompanied by decreased hippocampal levels of CoQ9 and CoQ10, increased oxidative stress, and reduced antioxidant defenses (p < 0.05). Additionally, hippocampal PGC-1α, FNDC5 and BDNF expression levels were reduced (p < 0.05). CoQ10 treatment resulted in significant improvements in these neuropathological parameters (p < 0.05). These results imply that CoQ10 can counteract the behavioral, biochemical, and molecular disturbances characteristic of FM. The mechanism is suggested to involve stimulating the PGC-1α/FNDC5/BDNF cascade, which in turn reduces behavioral deficits linked to pain, depression, and cognitive function.