Considerable evidence shows critical roles of intracellular pathogenic events of Alzheimer's disease (AD). In particular, intracellular amyloid-β accumulation and oligomerization are early AD pathologic processes, which may lead to changes in inflammatory molecules and other AD-related pathological components. Curcumin and its analogs have been identified as potential drug candidates for AD. However, the effects of curcumin on intracellular AD pathologic processes remain largely unknown. Here we utilized a recently developed nanoplasmonic fiber tip probe (nFTP) technology and investigated whether curcumin leads to intracellular AD pathologic changes. We showed that our nFTP technology could robustly detect intracellular AD-related protein changes caused by a well-known inflammation inducer and a familial AD mutation. Intriguingly, curcumin remarkably reduced the level of intracellular oligomers while modestly reduced the level of an inflammatory cytokine. Thus, our results provided evidence that curcumin's mechanism of action in attenuating AD pathology is through a major role of decreasing oligomerization.