Traditional medicine claims that various components of thePhoenix dactylifera(date plant) can be used to treat memory loss, fever, inflammation, loss of consciousness, and nerve disorders. The present study aims to evaluate the effectiveness ofPhoenix dactyliferafruit extracts (PDF) against rat sickness behaviour caused by lipopolysaccharide (LPS) by assessing behavioural and biochemical parameters. PDF was prepared by extracting dry fruits ofP. dactyliferawith a methanol:water (4:1,v/v) mixture. The PDF was evaluated for phenolic and flavonoid content and HPLC analysis of quercetin estimation. Adult Wistar rats were treated with LPS, PDF + LPS and dexamethasone + LPS. Water and food intake, behavioural tests such as locomotor activity, tail suspension and forced swim tests were conducted. Furthermore, alanine transaminase (ALT) and aspartate transaminase (AST) were estimated in plasma and malondialdehyde (MDA), reduced glutathione (GSH), nitrite, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), were estimated in the brain. PDF ameliorated LPS-induced sickness behaviour by reducing MDA, nitrite, IL-6, and TNF-α levels and improving GSH, behavioural alteration, water and food intake in the treated rats. In the plasma of the treated rats, PDF also decreased the levels of ALT and AST. The outcomes demonstrated the efficacy of PDF in reducing the sickness behaviour caused by LPS in rats. The authors believe that this study will provide the groundwork for future research to better understand the underlying mechanisms of action and therapeutic efficacy.