Periodontitis is a common chronic inflammation that often occurs in adults. Circular RNAs (circRNAs) play a vital role in inflammation-related diseases. However, the role and potential basis of hsa_circ_0085289 in periodontitis remain unknown. Periodontal ligament cells (PDLCs) were exposed to lipopolysaccharide (LPS) to mimic periodontitis. The levels of circ_0085289, let-7f-5p, and suppressor of cytokine signaling 6 (SOCS6) were determined using qRT-PCR and western blot. The release of inflammatory cytokines was measured via enzyme-linked immunosorbent assay (ELISA). Cell viability and apoptosis were determined using Cell Counting Kit-8, flow cytometry, Caspase-3 Assay Kit, and western blot assays. The association between let-7f-5p and circ_0085289/SOCS6 was validated via dual-luciferase reporter, RNA pull-down, and RIP assays. Circ_0085289 and SOCS6 levels were reduced, and let-7f-5p level was increased in periodontitis patients and LPS-treated PDLCs. LPS stimulation caused PDLC injury and circ_0085289 downregulation. Moreover, circ_0085289 upregulation or let-7f-5p downregulation diminished LPS-triggered PDLC injury. Besides, circ_0085289 promoted SOCS6 expression by absorbing let-7f-5p. Circ_0085289 alleviated LPS-stimulated PDLC injury via targeting let-7f-5p. Moreover, let-7f-5p targeted SOCS6 to affect LPS-resulted PDLC injury. Circ_0085289 alleviated PDLC injury induced by LPS stimulation via modulating let-7f-5p/SOCS6 axis, suggesting a promising biomarker for periodontitis treatment.