By employing Raman scattering and X-ray diffraction techniques on antiferromagnetic Bi 2.1 Sr 1.9 CaCu 2 O 8+δ within the same pressure conditions, we tracked the evolution of the two-magnon spectrum and structural parameters under pressures of up to nearly 30 GPa. Consequently, we established the relationship between pressure, in-plane lattice parameter d, and superexchange interaction J as J ∼ d −(6.6±0.2) . Within the examined pressure range, this compound did not exhibit superconductivity, as determined by a sensitive magnetic measurement technique. Additionally, we observed phonon anomalies, suggesting possible disorder effects in Bi−O layers and reduced charge transfer from these layers, particularly above 10 GPa. We discuss the impacts of pressure and chemical doping on J and the structure, along with their implications for superconductivity.