Microsoft Defender for Office 365 vs Proofpoint Threat Protection: Side-by-Side Comparison (2026)

Microsoft Defender for Office 365

Mid-market and enterprise teams already operating Microsoft 365 should standardize on Defender for Office 365 because the integration depth eliminates the detection gaps that plague bolt-on email security tools, particularly in Teams and SharePoint where most modern attacks now land. The platform's automated Business Email Compromise disruption with user disabling and device isolation actually stops lateral movement in real time rather than just flagging suspicious mail. Skip this if your organization runs primarily on Gmail or Slack; the advantage collapses outside the Microsoft ecosystem, and you'll find cheaper, more agile options elsewhere.

Proofpoint Threat Protection

Mid-market and enterprise security teams fighting phishing and business email compromise will see the fastest ROI with Proofpoint Threat Protection because its AI detection catches account takeover attempts that signature-based filters miss, and the integrated security awareness training closes the human gap that email-only tools ignore. The platform covers seven NIST CSF 2.0 functions including Continuous Monitoring and Adverse Event Analysis, which means detection and response workflows are built in rather than bolted on. Skip this if your organization needs best-of-breed CASB or insider threat capabilities independent of email context; those modules exist but are secondary to what Proofpoint does best.