"At least 20,000" protesters joined the march near the town of Döttingen and the Beznau nuclear power plant, Switzerland's oldest, police and organizers said.
"It's the biggest demonstration in Switzerland against nuclear power since the Fukushima accident (in Japan)," spokeswoman for "Sortons du nuclaire"
Maude Poirier told AFP. "These thousands of people who have come are sending a strong signal to the Swiss authorities.
"This shows that we are not a minority, that it's not only the Greens" calling for an end to nuclear power, she said.
The group said protesters had also come from Germany, Austria and France.
During the march, demonstrators held banners with slogans like: "No thanks to nuclear."
The Swiss government is set to decide Wednesday whether to mothball the country's five nuclear power plants.
After the March 11 earthquake and tsunami in Japan triggered the world's worst nuclear disaster since Chernobyl 25 years ago, Switzerland was the first country on March 14 to suspend plans to replace its ageing nuclear power plants.