Friends of the Canadian Wheat Board filed a class-action lawsuit in 2012 over legislation that removed the marketing agency's monopoly on western wheat and barley sales.
It sought leave to appeal after a lower court struck down the main parts of the class-action.
Stewart Wells, a spokesman for the group, said they are disappointed the legal system can't fully hold Ottawa accountable for what he calls the "confiscation and destruction of the wheat board" in 2011.
"The legal system has quite simply not been able to afford justice to western Canadian farmers so far," Wells said Thursday from Swift Current, Sask.
Wells said the group will continue with part of the lawsuit that focuses on wheat board money that the group claims was misallocated in the 2011-12 crop year.
Last fall the Federal Court of Appeal upheld the right of the Friends of the Canadian Wheat Board to proceed with that part of the lawsuit.
Agriculture Minister Gerry Ritz said the Supreme Court's decision not to hear the appeal upholds western Canadian farmers' right to marketing freedom.
"The overwhelming majority of farmers have embraced the new economic opportunities created by marketing freedom and are taking Canadian agriculture to record heights," Ritz said in a statement from Ottawa.
"Marketing freedom is and will remain the law of the land."
The federal government plans to privatize the wheat board before August 2017.
Wells said since the federal government changed the marketing system, western grain farmers have lost billions of dollars.
He said in 2014-15 alone, the spread between port prices and farm gate prices increased, causing losses estimated at $3 billion.