The antioxidant activities and effects of selected phenolic acids (ferulic, caffeic, p-coumaric and chlorogenic acids) on enzymes (ATPdase, ecto-5′ nucleotidase, phosphodiesterase-5′ and Na⁺/K⁺ ATPase) of the purinergic signalling in isolated rat brain were assessed. The antioxidant properties as typified by the DPPH and ABTS radical scavenging ability as well as inhibition of thiobarbituric acid reactive substances (TBARS) production in isolated rat brain revealed that chlorogenic acid had the highest antioxidant effect. Furthermore, ferulic acid had the highest Na⁺/K⁺-ATPase (IC₅₀ = 3.48 μM) stimulatory activity, as well as the highest ecto-5′ nucleotidase (IC₅₀ = 6.22 μM) inhibitory activity. In addition, chlorogenic acid had the highest phosphodiesterase-5′ (IC₅₀ = 21.03 μM) inhibitory activity while p-coumaric acid caused the highest inhibition of ATPdase (IC₅₀ = 17.56 μM) activity. This study revealed that the phenolic acids altered critical enzymes of the purinergic signaling in addition to their antioxidant properties thus, suggesting their possible neuromodulatory effects.