Isolationism inadvertently harmed the United States by making it easier for international problems to get out of hand. Without active American involvement on the international stage, no other country had the power and the influence necessary to prevent or manage the series of crises that swept across the world during the 1930s.
Without the United States onboard, the League of Nations proved singularly ineffectual in dealing with issues such as German expansionism and Japanese and Italian imperialism. Although such issues didn't directly affect the United States at first, they stored up all kinds of problems that the country would have to face sooner or later.
If the United States had pursued a more active foreign policy during the 1920s and early 1930s, then perhaps it would've been possible to nip such problems in the bud. As it was, German Nazis, Italian Fascists, and Japanese imperialists felt emboldened to do as they pleased, safe in the knowledge that the Americans would do little or nothing to stop them.
As it was, isolationism meant that by the time the United States entered World War II in 1941, the task of defeating the Axis powers was much greater than it would've been had a more active foreign policy been pursued earlier. And though the United States and her Allies prevailed in the conflict, this was at a considerable cost in human lives—lives that may well have been saved had isolationism not been pursued during such a dangerous period in world history.