The objective of our present study is to scrutinize the analgesic and anti-inflammatory potentials of essential oil of Eucalyptus camaldulensis leaf using different in vivo assay models at doses of 100, 200, and 400 mg/kg body weight. Twenty chemical compounds, which were isolated from the leaves essential oil of E. camaldulensis, were docked using AutodockVina against cyclooxygenase 2, tumor necrosis factor-α, and interleukin-1β convertase to elucidate the analgesic and anti-inflammatory activity. The essential oil of E. camaldulensis exhibited noteworthy analgesic activities in the writhing test. In the tail immersion and hot-plate test, the essential oil significantly extended the latency period. The number of licks in the formalin-induced paw licking test was markedly reduced following essential oil administration. In addition, E. camaldulensis essential oil revealed notable anti-inflammatory responses in carrageenan-induced paw edema, xylene induced ear edema and cotton pellet induced granuloma methods. Among 20 compounds, 5 (cis-sabinol, globulol, α-eudesmol, β-eudesmol, and γ-eudesmol) showed better binding for cyclooxygenase-2 while β-eudesmol exhibited higher affinity for TNFα than that of TNF-alpha-IN-1 and standard drug. In the case of interleukin 1β convertase, maximum affinity was shown by α-eudesmol than the synthetic drug belnacasan. Chemical components of the essential oil interacted with diverse amino acid residues which were similar to the natural substrate and standard drugs. In conclusion, E. camaldulensis essential oil can be an effective source of analgesic and anti-inflammatory treatment and additional modification and docking studies will be required to justify the efficiency of globulol, α-eudesmol, β-eudesmol, and γ-eudesmol.