If we are looking only at the actual voyages that Christopher Columbus himself made, the effects were rather minimal. Columbus made only four voyages to the New World. He only reached the mainland of Central America on his fourth voyage, having reached various islands on the other voyages. This means that he and his men had direct contact with a very few natives of the New World. Those who did come in contact with Columbus were affected in a negative way. Many were enslaved or forced to work for the Spanish. Some were killed. In general, the people of the New World were typically abused by the Spanish.
However, if we look at the way the natives of the New World were affected by the “discovery” of their continent, the effects are much greater. Columbus’ voyages paved the way for European exploration and domination of the New World. In North America, this largely meant that the natives were killed or pushed off their land. In South America, it meant that their cultures were to be absorbed into Spanish culture. The natives of South America and Central America were not killed or forced off their land like the North American Indians, but they were largely forced to accept Spanish culture and they became the lowest class of Spanish colonial society.
In these ways, the long-term, or indirect impacts of Columbus’s voyages on the natives of the New World were very severe.