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Background: The flower of Acmella uliginosa (AU) (Sw.) Cass., a naturally grown herb in India, is consumed as a natural painkiller for its notable analgesic properties. Objective: The objective of the study was to establish the role of AU flower methanolic extract in antinociception and its neuromodulatory activities to assess any disadvantage of the drug akin to opioids. Materials and Methods: In experimental rats, plant flower extracts were fed at a dose of 100 mg and 200 mg/kg body weight (BW) for 14 days. Analgesic activity was evaluated through formalin-induced paw licking test. T-maze, novel object recognition (NOR), and rotarod tests were done to assess the role of the extract in memory alteration and neuromotor coordination, respectively. Acetylcholinesterase (AChE), reduced glutathione (GSH), and superoxide dismutase (SOD) activity from the brain homogenates were done to assess the induced oxidative stress. Results: The plant proved to be a promising analgesic when fed orally up to 200 mg/kg BW dose. No acute toxicity was seen up to 1000 mg/kg. In the T-maze test, extract-fed animals showed a reduction in food searching time. In NOR test, the discrimination index between new and familiar objects was high in extract-fed animals compared to standard group. In rotarod test, the extract did not alter the neuromotor coordination. AChE, GSH, and SOD activities were normal in extract-treated animals. Conclusion: Memory alteration and oxidative stress are two major drawbacks associated with opioid drugs. Our results indicate that the AU flower methanolic extract qualifies as a potent painkiller and overcomes the disadvantages of opioid analgesics. [ABSTRACT FROM AUTHOR]