The main reason for refusing to ratify the Treaty of Versailles was it would mean the US would enter into the League of Nations. Senators believed that doing so meant giving up some of the United States' own sovereignty and could commit the US to defend other nations' security rather than its own.
The United States never joined the League of Nations, in spite of the fact that an organization such as the League of Nations was the signature idea of US President Woodrow Wilson. He had laid out 14 Points for establishing and maintaining world peace following the Great War (World War I). Point #14 was the establishment of an international peacekeeping association. The Treaty of Versailles adopted that idea, but back home in the United States, there was not support for involving America in any association that could diminish US sovereignty over its own affairs or involve the US again in wars beyond those pertinent to the United States' own national security. Because of its objections to membership in the League of Nations, the United States Senate refused to ratify the Treaty of Versailles.