The proliferation of open-source software (OSS) has made software supply chains prime targets for attacks like Package Confusion, where adversaries publish malicious packages with names deceptively similar to legitimate ones. To protect against such attacks and safeguard the use of OSS, multiple confusion detection methods have been proposed. However, existing methods are limited to single-signal retrieval strategies (relying solely on lexical or semantic metrics), struggle with high false positive rates (FPR), and are vulnerable to adversarial evasion. Critically, as content-agnostic approaches, they fundamentally fail to distinguish benign packages with high naming similarity from malicious, code-dissimilar impersonations, leading to persistent high FPR. To address these limitations, we introduce AgentGuard, a novel multi-agents based framework for package confusion detection. Specifically, it first discovers potential confusion targets using fine-tuned word embedding models with hybrid similarity search. After that, It subsequently evaluates risk via a fused machine learning model that uniquely combines: (1) a multi-dimensional metadata group and (2) a novel package content analysis group, to reduce the FPR and mitigate the impact of adversarial evasion. To assess the effectiveness of AgentGuard, we evaluate it on challenging ConfuDB and NeupaneDB datasets. Our results demonstrate that AgentGuard significantly outperforms state-of-the-art baselines, ConfuGuard and Typomind, improving precision by 12\%-49\% while simultaneously reducing the FPR by 11\%-35\%, and effectively discovers the confused package.