Alzheimer’s disease is the most widespread advancing neurodegenerative disorder, and it is estimated that more than 50 million people have been affected worldwide. It is characterized by dementia, loss of sensory and motor function and difficulty in performing work. NMDA antagonists and acetylcholinesterase inhibitors are currently being used as treatment options for AD, but the treatment would not decline the disease progression as well as neurodegeneration. We used a unique humic acid and fulvic acid mixture in the current investigation for the treatment of amyloid-β intoxicated Alzheimer’s in vitro model in SH-SY5Y cell line. Humic acid and fulvic acids are organic substances produced by microorganisms from the biomass such as dead matter of animals and plants. Both the components were used in the 1:1 ratio against AD-induced cell line with optimum concentration 50 µM/mL of each compound. The inflammatory mediators like Reactive Oxygen Species (ROS) were estimated using flow cytometry-H2DCFDA staining assay and cytokines such as TNF-α and IL-1β levels were estimated using ELISA. The results obtained from present study indicate that humic acid, fulvic acids, and their novel combinations lessen ROS, cytokines level and decrease apoptosis levels, thereby exhibiting neuroprotective mechanism via inhibiting neuro-inflammatory pathway in AD. © 2023 Elsevier B.V., All rights reserved.